Syt1

Summary

Gene Symbol: Syt1
Description: synaptotagmin I
Alias: P65, synaptotagmin 1, synaptotagmin-1, sytI
Species: rat

Top Publications

  1. doi The cytoplasmic C2A domain of synaptotagmin shows sequence specific interaction with its own mRNA
    Sunitha S Sukumaran
    Division of Molecular Medicine, Sree Chitra Tirunal Institute for Medical Sciences and Technology, BMT Wing, Poojapura, Trivandrum, Kerala 695012, India
    Biochem Biophys Res Commun 373:509-14. 2008
  2. pmc Cis- and trans-membrane interactions of synaptotagmin-1
    Wensi Vennekate
    Research Group Biomolecular Spectroscopy and Single Molecule Detection and Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany
    Proc Natl Acad Sci U S A 109:11037-42. 2012
  3. pmc Post-translational modifications and lipid binding profile of insect cell-expressed full-length mammalian synaptotagmin 1
    Marija Vrljic
    Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 5432, USA
    Biochemistry 50:9998-10012. 2011
  4. pmc Release mode of large and small dense-core vesicles specified by different synaptotagmin isoforms in PC12 cells
    Zhen Zhang
    Department of Physiology, University of Wisconsin School of Medical and Public Health, Madison, WI 53706, USA
    Mol Biol Cell 22:2324-36. 2011
  5. pmc Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1
    Han Ki Lee
    Department of Physics, KAIST, Daejeon 305 701, South Korea
    Science 328:760-3. 2010
  6. ncbi C-terminal ECFP fusion impairs synaptotagmin 1 function: crowding out synaptotagmin 1
    Weiping Han
    Center for Basic Neuroscience, The Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 280:5089-100. 2005
  7. pmc The calcium-dependent and calcium-independent membrane binding of synaptotagmin 1: two modes of C2B binding
    Weiwei Kuo
    Department of Chemistry, McCormick Road, University of Virginia, Charlottesville, VA 22904 4319, USA
    J Mol Biol 387:284-94. 2009
  8. doi Differential distribution of synaptotagmin-1, -4, -7, and -9 in rat adrenal chromaffin cells
    Hidetada Matsuoka
    Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807 8555, Japan
    Cell Tissue Res 344:41-50. 2011
  9. pmc Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold
    Geert van den Bogaart
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Georg August University, 37077 Gottingen, Germany
    J Biol Chem 287:16447-53. 2012
  10. pmc Conformation and membrane position of the region linking the two C2 domains in synaptotagmin 1 by site-directed spin labeling
    Hao Huang
    Department of Chemistry and Biophysics Program, University of Virginia, Charlottesville, Virginia 22904 4319, USA
    Biochemistry 47:12380-8. 2008

Scientific Experts

  • Motojiro Yoshihara
  • Charles F Stevens
  • G J O Evans
  • Hiroshi Tokumaru
  • Yuan Cheng
  • Mitsunori Fukuda
  • Edwin R Chapman
  • David S Cafiso
  • Dawn Z Herrick
  • Jihong Bai
  • Weiwei Kuo
  • Meyer B Jackson
  • Ying Lai
  • Zhen Zhang
  • Reinhard Jahn
  • Hao Huang
  • Chih Tien Wang
  • Kara L Lynch
  • Geert van den Bogaart
  • Yeon Kyun Shin
  • Thomas C Sudhof
  • Michael C Chicka
  • Axel T Brunger
  • Sascha Martens
  • Sumiko Mochida
  • Demet Arac
  • H Y Yang
  • Wensi Vennekate
  • Camin Dean
  • Toshio Masumoto
  • Zengliu Su
  • F Mark Dunning
  • Alex L Lai
  • Marija Vrljic
  • Hidetada Matsuoka
  • Chen Wan
  • Sune M Christensen
  • Alan P Cooper
  • Ward C Tucker
  • Johnnie M Moore-Dotson
  • Huisheng Liu
  • Yasunori Yamamoto
  • Han Ki Lee
  • T C Sudhof
  • Jeffrey F Ellena
  • Veerappan Anbazhagan
  • Jaewon Ko
  • Anand Radhakrishnan
  • Paul W Howard
  • Enfu Hui
  • Jason B Papke
  • Amy B Harkins
  • Sunitha S Sukumaran
  • Hui Li
  • Eiko Kanno
  • Betul Bakkaloglu
  • Akhil Bhalla
  • Thomas F J Martin
  • Harvey T McMahon
  • Dan Zhu
  • Chin Yu
  • William H Roden
  • Zheng Xing Wu
  • Tao Xu
  • Katrin I Willig
  • Rajesh Khanna
  • Xiong Xiong
  • Grigory Krapivinsky
  • Anne Hinderliter
  • Josep Rizo
  • Dakshinamurthy Rajalingam
  • I Fernandez
  • Amanda E Schivell
  • Elisabeth Rufener
  • Weiping Han
  • Ryoko Kohno
  • Anton Maximov
  • Xue Han
  • Ok Ho Shin
  • Angela Willshaw
  • Colin Rickman
  • Byung Hoon Lee
  • David A Richards
  • James A Ernst
  • Roy Cohen
  • Min Dong
  • Ulrich Heindel
  • Ping Wang
  • Ying Jie Lu
  • Klaus Schulten

Detail Information

Publications83

  1. doi The cytoplasmic C2A domain of synaptotagmin shows sequence specific interaction with its own mRNA
    Sunitha S Sukumaran
    Division of Molecular Medicine, Sree Chitra Tirunal Institute for Medical Sciences and Technology, BMT Wing, Poojapura, Trivandrum, Kerala 695012, India
    Biochem Biophys Res Commun 373:509-14. 2008
    Synaptotagmin-1 (Syt1) is essential in Ca(2+)-dependent neurotransmitter release, but its expression regulation is unknown...
  2. pmc Cis- and trans-membrane interactions of synaptotagmin-1
    Wensi Vennekate
    Research Group Biomolecular Spectroscopy and Single Molecule Detection and Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany
    Proc Natl Acad Sci U S A 109:11037-42. 2012
    ..We conclude that trans-interactions of synaptotagmin considered to be essential for its function are controlled by a delicate balance between cis- and trans-binding, which may play an important modulatory role in synaptic transmission...
  3. pmc Post-translational modifications and lipid binding profile of insect cell-expressed full-length mammalian synaptotagmin 1
    Marija Vrljic
    Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 5432, USA
    Biochemistry 50:9998-10012. 2011
    b>Synaptotagmin 1 (Syt1) is a Ca(2+) sensor for SNARE-mediated, Ca(2+)-triggered synaptic vesicle fusion in neurons. It is composed of luminal, transmembrane, linker, and two Ca(2+)-binding (C2) domains...
  4. pmc Release mode of large and small dense-core vesicles specified by different synaptotagmin isoforms in PC12 cells
    Zhen Zhang
    Department of Physiology, University of Wisconsin School of Medical and Public Health, Madison, WI 53706, USA
    Mol Biol Cell 22:2324-36. 2011
    ..Thus synaptotagmin isoforms can provide multiple levels of control in the release of different molecules from the same cell...
  5. pmc Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1
    Han Ki Lee
    Department of Physics, KAIST, Daejeon 305 701, South Korea
    Science 328:760-3. 2010
    In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise...
  6. ncbi C-terminal ECFP fusion impairs synaptotagmin 1 function: crowding out synaptotagmin 1
    Weiping Han
    Center for Basic Neuroscience, The Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9111, USA
    J Biol Chem 280:5089-100. 2005
    To allow the monitoring of synaptotagmin 1 trafficking in vivo, we generated transgenic mice expressing a synaptotagmin 1-enhanced cyan fluorescent protein (ECFP) fusion protein under control of the Thy1 promoter...
  7. pmc The calcium-dependent and calcium-independent membrane binding of synaptotagmin 1: two modes of C2B binding
    Weiwei Kuo
    Department of Chemistry, McCormick Road, University of Virginia, Charlottesville, VA 22904 4319, USA
    J Mol Biol 387:284-94. 2009
    The Ca2+-independent membrane interactions of the soluble C2 domains from synaptotagmin 1 (syt1) were characterized using a combination of site-directed spin labeling and vesicle sedimentation...
  8. doi Differential distribution of synaptotagmin-1, -4, -7, and -9 in rat adrenal chromaffin cells
    Hidetada Matsuoka
    Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807 8555, Japan
    Cell Tissue Res 344:41-50. 2011
    ..We conclude that LDCVs mainly contain Syt 7, whereas SLMVs contain Syt 1, but not Syt 7, in rat and bovine chromaffin cells...
  9. pmc Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold
    Geert van den Bogaart
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Georg August University, 37077 Gottingen, Germany
    J Biol Chem 287:16447-53. 2012
    ..Thus, our data show that PIP(2) makes synaptotagmin-1 >40-fold more sensitive to Ca(2+). This interplay between Ca(2+), synaptotagmin-1, and PIP(2) is crucial for neurotransmitter release...
  10. pmc Conformation and membrane position of the region linking the two C2 domains in synaptotagmin 1 by site-directed spin labeling
    Hao Huang
    Department of Chemistry and Biophysics Program, University of Virginia, Charlottesville, Virginia 22904 4319, USA
    Biochemistry 47:12380-8. 2008
    b>Synaptotagmin 1 (syt1) is an integral membrane protein localized on the synaptic vesicle that acts as the Ca(2+) sensor for neuronal exocytosis...
  11. doi The importance of an asymmetric distribution of acidic lipids for synaptotagmin 1 function as a Ca2+ sensor
    Ying Lai
    Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA
    Biochem J 443:223-9. 2012
    Syt1 (synaptotagmin 1) is a major Ca2+ sensor for synaptic vesicle fusion...
  12. doi Effect of thyroxine on SNARE complex and synaptotagmin-1 expression in the prefrontal cortex of rats with adult-onset hypothyroidism
    H Y Yang
    Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Anhui, China
    J Endocrinol Invest 35:312-6. 2012
    ..Our findings indicate that dysregulation of SNARE complex and syt-1 in PFC of adult-onset hypothyroidism can be restored by T(4) treatment...
  13. pmc Regulation of exocytosis and fusion pores by synaptotagmin-effector interactions
    Zhen Zhang
    National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
    Mol Biol Cell 21:2821-31. 2010
    ..This associates the syt-PS interaction with two distinct kinetic steps in Ca(2+) triggered exocytosis and supports a role for the syt-PS interaction in stabilizing open fusion pores...
  14. pmc Synaptotagmin 1 and SNAREs form a complex that is structurally heterogeneous
    Alex L Lai
    Department of Chemistry, Biophysics Program and Center for Membrane Biology at the University of Virginia, Charlottesville, VA 22904 4319, USA
    J Mol Biol 405:696-706. 2011
    b>Synaptotagmin 1 (syt1) functions as a Ca(2+)-sensor for neuronal exocytosis...
  15. pmc Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells
    Min Dong
    Department of Physiology, University of Wisconsin, Madison, Madison, WI 53706, USA
    J Cell Biol 162:1293-303. 2003
    ..Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT/B...
  16. ncbi Fusion pore dynamics are regulated by synaptotagmin*t-SNARE interactions
    Jihong Bai
    Department of Physiology, University of Wisconsin, Madison, WI 53706, USA
    Neuron 41:929-42. 2004
    ..Thus, the final step of Ca2+-triggered exocytosis is regulated, at least in part, by direct contacts between syt and SNAP-25/syntaxin...
  17. ncbi Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs
    Ward C Tucker
    Department of Physiology, University of Wisconsin, Madison, WI 53706, USA
    Science 304:435-8. 2004
    ..Stimulation of fusion was abolished by disrupting the Ca2+-binding activity, or by severing the tandem C2 domains, of syt. Thus, syt and SNAREs are likely to represent the minimal protein complement for Ca2+-triggered exocytosis...
  18. pmc Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms
    Akhil Bhalla
    Howard Hughes Medical Institute, and Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA
    J Biol Chem 283:21799-807. 2008
    ..Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other...
  19. ncbi Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids
    Demet Arac
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Nat Struct Mol Biol 13:209-17. 2006
    ..We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C(2)B domain...
  20. ncbi Position of synaptotagmin I at the membrane interface: cooperative interactions of tandem C2 domains
    Dawn Z Herrick
    Department of Chemistry and Biophysics Program, University of Virginia, Charlottesville, USA
    Biochemistry 45:9668-74. 2006
    ..These data indicate that C2A and C2B do not act independently but influence their mutual membrane penetration. This may explain the occurrence of multiple C2 domains in proteins that function in membrane trafficking and repair...
  21. ncbi How synaptotagmin promotes membrane fusion
    Sascha Martens
    Medical Research Council Laboratory of Molecular Biology, Hills Road, CB2 0QH Cambridge, UK
    Science 316:1205-8. 2007
    ..Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion...
  22. pmc Synaptotagmin-1 utilizes membrane bending and SNARE binding to drive fusion pore expansion
    Kara L Lynch
    Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA
    Mol Biol Cell 19:5093-103. 2008
    ..The results indicate that Syt-1 uses both Ca(2+)-dependent membrane insertion and SNARE binding to drive fusion pore expansion...
  23. doi Direct interaction of SNARE complex binding protein synaphin/complexin with calcium sensor synaptotagmin 1
    Hiroshi Tokumaru
    Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, Kagawa 769 2193, Japan
    Brain Cell Biol 36:173-89. 2008
    ..Here, we show that synaphin directly binds to synaptotagmin 1, a major Ca(2+) sensor for fast neurotransmitter release, in a 1:1 stoichiometry...
  24. pmc Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation
    Jaewon Ko
    Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, CA 94304 5543, USA
    EMBO J 28:3244-55. 2009
    ..Thus, neuroligin-1 performs diverse synaptic functions by mechanisms that include as essential components of alpha-neurexin binding and neuroligin dimerization, but extend beyond these activities...
  25. pmc Tomosyn inhibits synaptotagmin-1-mediated step of Ca2+-dependent neurotransmitter release through its N-terminal WD40 repeats
    Yasunori Yamamoto
    Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    J Biol Chem 285:40943-55. 2010
    ..These results suggest that the interplay between tomosyn and synaptotagmin-1 underlies inhibitory control of Ca(2+)-dependent neurotransmitter release...
  26. pmc Unexpected Ca2+-binding properties of synaptotagmin 9
    Ok Ho Shin
    Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, Dallas, TX 75390 9111, USA
    Proc Natl Acad Sci U S A 101:2554-9. 2004
    b>Synaptotagmin 1 (Syt 1) functions as an essential Ca2+ sensor for the fast but not slow component of Ca2+-triggered exocytosis...
  27. ncbi Palmitoylation sites and processing of synaptotagmin I, the putative calcium sensor for neurosecretion
    Ulrich Heindel
    Department of Immunology and Molecular Biology, Veterinary Medical Faculty, Free University Berlin, Philippstrasse 13, Germany
    FEBS Lett 544:57-62. 2003
    ..No significant cleavage of [(3)H]palmitate from synaptotagmin was observed in pulse-chase experiments. This indicates that the majority of fatty acids are structural rather than dynamic components...
  28. ncbi PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane
    Jihong Bai
    Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA
    Nat Struct Mol Biol 11:36-44. 2004
    ..We propose that syt-PIP2 interactions are involved in exocytosis by facilitating the close apposition of the vesicle and target membrane on rapid time scales in response to Ca2+...
  29. ncbi Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 cells
    Mitsunori Fukuda
    Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN The Institute of Physical and Chemical Research, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    J Biol Chem 277:4601-4. 2002
    ..Our results support the idea that Syt family proteins that co-reside on secretory vesicles may function cooperatively and redundantly as potential Ca(2+) sensors for exocytosis...
  30. pmc Phosphatidylinositol 4,5-bisphosphate alters synaptotagmin 1 membrane docking and drives opposing bilayers closer together
    Weiwei Kuo
    Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, Virginia 22904 4319, United States
    Biochemistry 50:2633-41. 2011
    b>Synaptotagmin 1 (syt1) is a synaptic vesicle-anchored membrane protein that acts as the calcium sensor for the synchronous component of neuronal exocytosis...
  31. ncbi Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells
    Kara L Lynch
    Department of Biochemistry, 433 Babcock Drive, University of Wisconsin, Madison, WI 53706, USA
    J Cell Sci 120:617-27. 2007
    ..The downregulation of synaptotagmin I but not synaptotagmin IX impaired compensatory vesicle endocytosis, which revealed a lack of isoform redundancy and functional specialization of synaptotagmin I for endocytic retrieval...
  32. ncbi Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine
    I Fernandez
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Neuron 32:1057-69. 2001
    b>Synaptotagmin 1 probably functions as a Ca2+ sensor in neurotransmitter release via its two C2-domains, but no common Ca2+-dependent activity that could underlie a cooperative action between them has been described...
  33. pmc Solution and membrane-bound conformations of the tandem C2A and C2B domains of synaptotagmin 1: Evidence for bilayer bridging
    Dawn Z Herrick
    Department of Chemistry and Biophysics, University of Virginia, Charlottesville, 22904 4319, USA
    J Mol Biol 390:913-23. 2009
    b>Synaptotagmin 1 (syt1) is a synaptic vesicle membrane protein that functions as the Ca(2)(+) sensor in neuronal exocytosis...
  34. ncbi Stable RNA interference of synaptotagmin I in PC12 cells results in differential regulation of transmitter release
    William H Roden
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA
    Am J Physiol Cell Physiol 293:C1742-52. 2007
    ..Electron micrographs show that large dense core vesicles are synthesized and available for release in cells that lack syt I. These results are consistent with syt I regulating differential release of transmitters...
  35. ncbi Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?
    X Shao
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas 75235, USA
    Biochemistry 37:16106-15. 1998
    ..This mechanism may also be valid for other C2 domains that share the unusual ability to bind multiple Ca2+ ions in a tight cluster at the tip of the domain...
  36. ncbi The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission
    Charles F Stevens
    Molecular Neurobiology Laboratory, Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 39:299-308. 2003
    ..We conclude that neutralization of the negative charge at D232 by coordination of a calcium ion is necessary--but not sufficient--for fast neurotransmission at mammalian CNS synapses...
  37. ncbi STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis
    Katrin I Willig
    Departments of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany
    Nature 440:935-9. 2006
    ..Our study also demonstrates that questions involving cellular structures with dimensions of a few tens of nanometres can be resolved with conventional far-field optics and visible light...
  38. ncbi Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold
    R B Sutton
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235
    Cell 80:929-38. 1995
    ..Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C2-key motif...
  39. ncbi Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C
    M S Perin
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235
    Nature 345:260-3. 1990
    ..We now report that the cytoplasmic domain of p65, a synaptic vesicle-specific protein that binds calmodulin contains an internally repeated sequence that is ..
  40. ncbi Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate
    Colin Rickman
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    J Biol Chem 279:12574-9. 2004
    ..Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion...
  41. pmc Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation
    Chih Tien Wang
    Department of Physiology, University of Wisconsin, Madison, 53706, USA
    J Physiol 570:295-307. 2006
    ..The C2A and C2B domains of Syt I have different actions during these steps, and these actions may be linked to their distinctive effector interactions...
  42. ncbi Increased plasma membrane localization of O-glycosylation-deficient mutant of synaptotagmin I in PC12 cells
    Eiko Kanno
    Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba ku, Sendai, Miyagi, Japan
    J Neurosci Res 86:1036-43. 2008
    ..The results indicate that O-glycosylation, not N-glycosylation, is partially involved in efficient targeting of Syt I protein to dense-core vesicles in PC12 cells...
  43. pmc Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain
    Yuan Cheng
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Protein Sci 13:2665-72. 2004
    ..In the presence of Sr(2+), which is also capable of triggering exocytosis, but with lower efficiency, only one cation binding site (site 1) was occupied in the crystallographic structure...
  44. pmc The Ca2+ affinity of synaptotagmin 1 is markedly increased by a specific interaction of its C2B domain with phosphatidylinositol 4,5-bisphosphate
    Anand Radhakrishnan
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany
    J Biol Chem 284:25749-60. 2009
    The synaptic vesicle protein synaptotagmin 1 is thought to convey the calcium signal onto the core secretory machinery...
  45. ncbi Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin
    E R Chapman
    Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA
    J Biol Chem 273:32966-72. 1998
    ..These studies provide the first structural information regarding C2B target protein recognition and provide the means to selectively disrupt synaptotagmin-effector interactions for functional studies...
  46. ncbi Silence of synaptotagmin I in INS-1 cells inhibits fast exocytosis and fast endocytosis
    Xiong Xiong
    Institute of Biophysics and Biochemistry, Huazhong University of Science and Technology, Wuhan, PR China
    Biochem Biophys Res Commun 347:76-82. 2006
    ..We conclude that Syt I not only participates in the Ca(2+)-sensing of LDCV fusion with plasmalemma, but also plays a crucial role in fast endocytosis in INS-1 cells...
  47. pmc Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional screen
    Camin Dean
    Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA
    Mol Biol Cell 23:1715-27. 2012
    ..Hence most syt isoforms localize to distinct secretory organelles in both axons and dendrites and may regulate neuropeptide/neurotrophin release to modulate neuronal function...
  48. pmc Fusion pore formation and expansion induced by Ca2+ and synaptotagmin 1
    Ying Lai
    Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA
    Proc Natl Acad Sci U S A 110:1333-8. 2013
    ..However, efficient fusion pore formation and expansion require synaptotagmin 1 and Ca(2+)...
  49. doi Ca(2+)-independent syntaxin binding to the C(2)B effector region of synaptotagmin
    Toshio Masumoto
    Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2 5 1 Shikata cho, Kita ku, Okayama Shi, Okayama 700 8558, Japan
    Mol Cell Neurosci 49:1-8. 2012
    ....
  50. ncbi The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release
    Grigory Krapivinsky
    Howard Hughes Medical Institute, Cardiology, Children s Hospital Boston, 1309 Enders Building, 320 Longwood Avenue, Boston, MA, USA
    Neuron 52:485-96. 2006
    ..Targeted peptide interference of TRPM7's interaction with snapin affects the amplitudes and kinetics of postsynaptic EPSPs. Thus, vesicular TRPM7 channel activity is critical to neurotransmitter release in sympathetic neurons...
  51. ncbi Expression of synaptotagmin 1 in the taste buds of rat gustatory papillae
    Ryoko Kohno
    Division of Orofacial Functions and Orthodontics, Department of Biosciences, Science of Health Improvement, Kyushu Dental College, Kitakyushu, Japan
    Arch Histol Cytol 68:235-41. 2005
    ..Many kinds of synaptic vesicle proteins participate in synaptic vesicle cycles. One of these, synaptotagmin 1, binds Ca(2+) phospholipids with high affinity and plays a role in Ca(2+) regulated neurotransmitter release ..
  52. pmc Single vesicle assaying of SNARE-synaptotagmin-driven fusion reveals fast and slow modes of both docking and fusion and intrasample heterogeneity
    Sune M Christensen
    Bio Nanotechnology Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
    Biophys J 100:957-67. 2011
    ..The presence of several distinct docking and fusion pathways cannot be rationalized at this stage but may be related to intrasample heterogeneities, presumably in the form of lipid and/or protein composition...
  53. pmc Partitioning of synaptotagmin I C2 domains between liquid-ordered and liquid-disordered inner leaflet lipid phases
    Chen Wan
    Center for Membrane Biology, Department of Molecular Physiology and Biological Physics, University of Virginia, Snyder Building, P O Box 800886, Charlottesville, Virginia 22908, United States
    Biochemistry 50:2478-85. 2011
    ..Accordingly, PS prefers the liquid-disordered phase over the liquid-ordered phase by ∼2-fold, but PIP(2) has an up to 3-fold preference for the liquid-disordered phase...
  54. ncbi SV2A and SV2C contain a unique synaptotagmin-binding site
    Amanda E Schivell
    Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195, USA
    Mol Cell Neurosci 29:56-64. 2005
    ..These observations implicate the SV2-synaptotagmin interaction in regulated exocytosis and suggest that SV2A and SV2C, via their additional synaptotagmin binding site, function differently than SV2B...
  55. doi Synaptotagmins I and II in the developing rat auditory brainstem: Synaptotagmin I is transiently expressed in glutamate-releasing immature inhibitory terminals
    Alan P Cooper
    Neuroscience Graduate Program, McMaster University, Hamilton, Ontario L8S 4K1 Canada
    J Comp Neurol 519:2417-33. 2011
    ..We have found that synaptotagmin 1 is indeed expressed transiently in the immature auditory brainstem, most highly in those areas that receive ..
  56. ncbi Synaptotagmin I and IX function redundantly in controlling fusion pore of large dense core vesicles
    Dan Zhu
    Key Laboratory of Molecular Biophysics Huazhong University of Science and Technology, Ministry of Education, and Joint Laboratory of Institute of Biophysics, Huazhong University of Science and Technology, Wuhan 430074, PR China
    Biochem Biophys Res Commun 361:922-7. 2007
    ..Down-regulation of both Syt I and Syt IX renders more fusion in the kiss-and-run mode. We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells...
  57. ncbi The COOH terminus of synaptotagmin mediates interaction with the neurexins
    M S Perin
    Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
    J Biol Chem 269:8576-81. 1994
    ..I propose that the carboxyl terminus of synaptotagmin binds to the carboxyl terminus of the neurexins and that this interaction may mediate docking of synaptic vesicles or modulation of neurotransmitter release...
  58. doi A residue-level investigation of the equilibrium unfolding of the C2A domain of synaptotagmin 1
    Veerappan Anbazhagan
    Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan, ROC
    Arch Biochem Biophys 490:158-62. 2009
    ..to be released in response to cellular stress conditions through formation of a multi-protein complex with synaptotagmin 1 and S100A13...
  59. ncbi Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins
    C Li
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA
    Nature 375:594-9. 1995
    ..The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs from that of Syt III and VII (< 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)..
  60. ncbi Membrane-bound orientation and position of the synaptotagmin C2B domain determined by site-directed spin labeling
    Elisabeth Rufener
    Department of Chemistry and Biophysics Program, University of Virginia, Charlottesville, Virginia 22904 4319, USA
    Biochemistry 44:18-28. 2005
    ..EPR spectroscopy indicates that the C2B domain has different interactions with PC/PS membranes containing 1 mol % phosphatidylinositol 4,5-bisphosphate...
  61. pmc Direct interaction between synaptotagmin and the intracellular loop I-II of neuronal voltage-sensitive sodium channels
    B Sampo
    Institut National de la Sante et de la Recherche Medicale, U464, Institut Jean Roche, Universite de la Mediterranee, Boulevard P Dramard, 13916 Marseille Cedex 20, France
    Proc Natl Acad Sci U S A 97:3666-71. 2000
    ..The Ca(2+)-regulated association between sodium channels and a protein implicated in vesicular fusion may have intriguing consequences for the establishment and regulation of neuronal excitability...
  62. ncbi Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner
    Ping Wang
    Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA
    J Biol Chem 278:47030-7. 2003
    ..These findings indicate that the tandem C2 domains of syt cooperate with one another to trigger release via loop-mediated electrostatic interactions with effector molecules...
  63. ncbi Transmembrane segments of syntaxin line the fusion pore of Ca2+-triggered exocytosis
    Xue Han
    Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA
    Science 304:289-92. 2004
    ..The residues that influenced fusion-pore flux lay along one face of an alpha-helical model. Thus, the fusion pore is formed at least in part by a circular arrangement of 5 to 8 Syx transmembrane segments in the plasma membrane...
  64. pmc Upregulation of synaptotagmin IV inhibits transmitter release in PC12 cells with targeted synaptotagmin I knockdown
    Johnnie M Moore-Dotson
    Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St, Louis, MO 63104, USA
    BMC Neurosci 11:104. 2010
    ..Recently, syt IV, an inducible Ca2+-independent isoform has been implicated in transmitter release. We postulated that the effects of syt IV on transmitter release are dependent on the expression of syt I...
  65. ncbi A plethora of presynaptic proteins associated with ATP-storing organelles in cultured astrocytes
    V Maienschein
    Biozentrum der J W Goethe Universität, AK Neurochemie, Frankfurt am Main, Germany
    Glia 26:233-44. 1999
    ..Our data suggest that messenger substances may be released from cultured astrocytes via receptor-mediated, Ca2+-dependent exocytosis...
  66. ncbi The C2A domain of synaptotagmin alters the kinetics of voltage-gated Ca2+ channels Ca(v)1.2 (Lc-type) and Ca(v)2.3 (R-type)
    Roy Cohen
    Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    J Biol Chem 278:9258-66. 2003
    ..It indicates that calcium-independent properties of Syt 1 regulate voltage-gated Ca2+ channels and contribute to the molecular events underlying transmitter release...
  67. pmc Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders
    Betul Bakkaloglu
    Program on Neurogenetics, Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA
    Am J Hum Genet 82:165-73. 2008
    ....
  68. doi NF-kappaB regulates prenatal stress-induced cognitive impairment in offspring rats
    Hui Li
    Xi an Jiaotong University
    Behav Neurosci 122:331-9. 2008
    ..used a rat model to study plasma levels of corticosterone and oxidative DNA damage (8-OH-dG), protein expression of P65/p50 NF-kappaB, and cognitive function in female and male offspring rats in middle pregnant stage and later pregnant ..
  69. ncbi WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding
    Byung Hoon Lee
    Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:741-51. 2004
    ..These findings provide a biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. Interruption of this regulatory pathway may disturb membrane events that regulate ion balance...
  70. pmc Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+
    Michael C Chicka
    Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, 1300 University Avenue, SMI 129, Madison, Wisconsin 53706, USA
    Nat Struct Mol Biol 15:827-35. 2008
    ..These findings demonstrate that Ca(2+) converts synaptotagmin from a clamp to a trigger for exocytosis...
  71. ncbi Inositol hexakisphosphate (InsP6) can weaken the Ca(2+)-dependent membrane binding of C2AB domain of synaptotagmin I
    Ying Jie Lu
    Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane, Tsinghua University, 100084, Beijing, PR China
    FEBS Lett 527:22-6. 2002
    ..The InsP6 binding notably weakened the Ca(2+)-dependent C2AB-membrane interaction, which suggests that InsP6 may act as a modulator of neurotransmitter release by altering the state of synaptotagmin-phospholipid interaction...
  72. pmc 'Fractional recovery' analysis of a presynaptic synaptotagmin 1-anchored endocytic protein complex
    Rajesh Khanna
    Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada
    PLoS ONE 1:e67. 2006
    The integral synaptic vesicle protein and putative calcium sensor, synaptotagmin 1 (STG), has also been implicated in synaptic vesicle (SV) recovery...
  73. ncbi Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin
    T Coppola
    Institut de Biologie Cellulaire et de Morphologie, University of Lausanne, 1005 Lausanne, Switzerland
    J Biol Chem 276:32756-62. 2001
    ..We propose that the Rab3 effector RIM is a scaffold protein that participates through its multiple binding partners in the docking and fusion of secretory vesicles at the release sites...
  74. ncbi High resolution structure, stability, and synaptotagmin binding of a truncated neuronal SNARE complex
    James A Ernst
    Howard Hughes Medical Institute, Stanford University, California 94305, USA
    J Biol Chem 278:8630-6. 2003
    ..The truncated SNARE complex is monomeric, and it retains binding to synaptotagmin I...
  75. ncbi Nadrin, a novel neuron-specific GTPase-activating protein involved in regulated exocytosis
    A Harada
    Department of Molecular Biodynamics, The Tokyo Metropolitan Institute of Medical Science Rinshoken, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    J Biol Chem 275:36885-91. 2000
    ..These results suggest that Nadrin plays a role in regulating Ca(2+)-dependent exocytosis, most likely by catalyzing GTPase activity of Rho family proteins and by inducing the reorganization of the cortical actin filaments...
  76. ncbi Functional properties of multiple synaptotagmins in brain
    B Ullrich
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235
    Neuron 13:1281-91. 1994
    ....
  77. ncbi Identification of a novel protein complex containing annexin A4, rabphilin and synaptotagmin
    Angela Willshaw
    The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, UK
    FEBS Lett 559:13-21. 2004
    ..we report the isolation and identification of a novel protein complex containing rabphilin, annexin A4 and synaptotagmin 1. We show that the rabphilin C2B domain interacts directly with the N-terminus of annexin A4 and mediates the ..
  78. ncbi Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin
    A E Schivell
    Graduate Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 271:27770-5. 1996
    ..Interaction is mediated by the cytoplasmic amino terminus of SV2A and the C2B domain of synaptotagmin. Our observations suggest a regulatory relationship between these two proteins...
  79. pmc Phosphorylation-dependent interaction of the synaptic vesicle proteins cysteine string protein and synaptotagmin I
    Gareth J O Evans
    The Physiological Laboratory, Department of Physiology, University of Liverpool, Crown St, Liverpool, L69 3BX, UK
    Biochem J 364:343-7. 2002
    ..Genetic studies have implicated each of these proteins in the Ca2+-dependency of exocytosis and, since CSP does not bind Ca2+, this novel interaction might explain the Ca2+-dependent actions of CSP...
  80. ncbi Complexins: cytosolic proteins that regulate SNAP receptor function
    H T McMahon
    Howard Hughes Medical Institute, University of Texas Southwestern Medical School, Dallas 75235, USA
    Cell 83:111-9. 1995
    ....
  81. pmc Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1
    Paul W Howard
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    Mol Endocrinol 23:1563-71. 2009
    ..In the present studies we have identified synaptotagmin I (Syt1) as a target gene for POU1F1 in GH(3) pituitary cells...
  82. ncbi The C2A domain of synaptotagmin exhibits a high binding affinity for copper: implications in the formation of the multiprotein FGF release complex
    Dakshinamurthy Rajalingam
    Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA
    Biochemistry 44:14431-42. 2005
    ..that is released into the extracellular compartment as a multiprotein complex consisting of S100A13, synaptotagmin (Syt1), and a hFGF-1 homodimer...