Gene Symbol: Syp
Description: synaptophysin
Alias: A230093K24Rik, AI848995, Syn, p38, synaptophysin, BM89 antigen, Syp I, major synaptic vesicle protein p38
Species: mouse
Products:     Syp

Top Publications

  1. de Castro B, De Jaeger X, Martins Silva C, Lima R, Amaral E, Menezes C, et al. The vesicular acetylcholine transporter is required for neuromuscular development and function. Mol Cell Biol. 2009;29:5238-50 pubmed publisher
    ..The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh. ..
  2. Sharma R, O Leary T, Fields C, Johnson D. Development of the outer retina in the mouse. Brain Res Dev Brain Res. 2003;145:93-105 pubmed
    ..the first appearance of photoreceptor neurites, development of the horizontal cell plexus, and development of synaptophysin immunoreactivity at this location...
  3. Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, et al. Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J Neurosci. 2009;29:10788-801 pubmed publisher
    ..We postulate that transsynaptic APP interaction modulates its synaptic function and that perturbed APP synaptic adhesion activity may contribute to synaptic dysfunction and AD pathogenesis. ..
  4. Brandon E, Lin W, D Amour K, Pizzo D, Dominguez B, Sugiura Y, et al. Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice. J Neurosci. 2003;23:539-49 pubmed
    ..These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses. ..
  5. Lin S, Maj M, Bezakova G, Magyar J, Brenner H, Ruegg M. Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice. Proc Natl Acad Sci U S A. 2008;105:11406-11 pubmed publisher
    ..Finally, they suggest a novel local function of ACh in stabilizing postsynaptic structures. ..
  6. Weiner J, Koo S, Nicolas S, Fraboulet S, Pfaff S, Pourquie O, et al. Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1. Mol Cell Neurosci. 2004;27:59-69 pubmed
    ..Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis...
  7. Misgeld T, Burgess R, Lewis R, Cunningham J, Lichtman J, Sanes J. Roles of neurotransmitter in synapse formation: development of neuromuscular junctions lacking choline acetyltransferase. Neuron. 2002;36:635-48 pubmed
    ..At subsequent stages, neurotransmission delays some steps in synaptic maturation but accelerates others. Thus, neurotransmission affects synaptogenesis from early stages and coordinates rather than drives synaptic maturation. ..
  8. Herbst R, Avetisova E, Burden S. Restoration of synapse formation in Musk mutant mice expressing a Musk/Trk chimeric receptor. Development. 2002;129:5449-60 pubmed
    ..Moreover, acetylcholine receptor clustering and motor terminal branching are restored in parallel, indicating that the extent of presynaptic differentiation is matched to the extent of postsynaptic differentiation. ..
  9. An M, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, et al. Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc Natl Acad Sci U S A. 2010;107:10702-7 pubmed publisher
    ..Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms. ..

More Information


  1. Feng G, Laskowski M, Feldheim D, Wang H, Lewis R, Frisen J, et al. Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers. Neuron. 2000;25:295-306 pubmed
    ..In addition, the rostrocaudal position of at least one motor pool is altered in ephrin-A5 mutant mice, indicating that ephrins affect nerve-muscle matching by intraspinal as well as intramuscular mechanisms. ..
  2. Okada K, Inoue A, Okada M, Murata Y, Kakuta S, Jigami T, et al. The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science. 2006;312:1802-5 pubmed publisher
    ..Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK...
  3. Serpinskaya A, Feng G, Sanes J, Craig A. Synapse formation by hippocampal neurons from agrin-deficient mice. Dev Biol. 1999;205:65-78 pubmed
    ..These results indicate that the z+ forms of agrin are dispensable for glutamatergic and GABAergic synaptic differentiation in the central nervous system. ..
  4. Kwon S, Chapman E. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons. Neuron. 2011;70:847-54 pubmed publisher
    Despite being the most abundant synaptic vesicle membrane protein, the function of synaptophysin remains enigmatic...
  5. Baudet C, Pozas E, Adameyko I, Andersson E, Ericson J, Ernfors P. Retrograde signaling onto Ret during motor nerve terminal maturation. J Neurosci. 2008;28:963-75 pubmed publisher
    ..Thus, Ret transmits a signal in motor nerve terminals that participate in the organization and maturation of presynaptic specializations during development and during regeneration in the adult. ..
  6. Eshkind L, Leube R. Mice lacking synaptophysin reproduce and form typical synaptic vesicles. Cell Tissue Res. 1995;282:423-33 pubmed
    b>Synaptophysin is one of the major integral membrane proteins of the small (30-50nm diameter) electron-translucent transmitter-containing vesicles in neurons and of similar vesicles in neuroendocrine cells...
  7. Liu Y, Padgett D, Takahashi M, Li H, Sayeed A, Teichert R, et al. Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development. 2008;135:1957-67 pubmed publisher
    ..These results demonstrate that the gamma-subunit is required for the formation of pre-patterned AChR clusters, which in turn play an essential role in determining the subsequent pattern of neuromuscular synaptogenesis. ..
  8. Banks G, Choy P, Lavidis N, Noakes P. Neuromuscular synapses mediate motor axon branching and motoneuron survival during the embryonic period of programmed cell death. Dev Biol. 2003;257:71-84 pubmed
    ..Thus, agrin-induced synaptic specializations are required for skeletal muscle to effectively control motoneuron numbers during embryonic development. ..
  9. Deuel T, Liu J, Corbo J, Yoo S, Rorke Adams L, Walsh C. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron. 2006;49:41-53 pubmed
    ..Dcx and Dclk may directly or indirectly regulate microtubule-based vesicle transport, a process critical to both neuronal migration and axon outgrowth. ..
  10. Schwander M, Shirasaki R, Pfaff S, Muller U. Beta1 integrins in muscle, but not in motor neurons, are required for skeletal muscle innervation. J Neurosci. 2004;24:8181-91 pubmed
    ..We conclude that Itgb1 expression in muscle, but not in motor neurons, is critical for NMJ development. ..
  11. Weatherbee S, Anderson K, Niswander L. LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development. 2006;133:4993-5000 pubmed
    ..The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes. ..
  12. Schmitt U, Tanimoto N, Seeliger M, Schaeffel F, Leube R. Detection of behavioral alterations and learning deficits in mice lacking synaptophysin. Neuroscience. 2009;162:234-43 pubmed publisher
    The integral membrane protein synaptophysin is one of the most abundant polypeptide components of synaptic vesicles...
  13. Yang X, Arber S, William C, Li L, Tanabe Y, Jessell T, et al. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399-410 pubmed
    ..Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation. ..
  14. Hallock P, Xu C, Park T, Neubert T, Curran T, Burden S. Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes Dev. 2010;24:2451-61 pubmed publisher
  15. Kneussel M, Brandstätter J, Laube B, Stahl S, Muller U, Betz H. Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice. J Neurosci. 1999;19:9289-97 pubmed
    ..In addition, gephyrin may be important for efficient membrane insertion and/or metabolic stabilization of inhibitory receptors at developing postsynaptic sites. ..
  16. Gautam M, Noakes P, Moscoso L, Rupp F, Scheller R, Merlie J, et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996;85:525-35 pubmed
  17. Shi L, Butt B, Ip F, Dai Y, Jiang L, Yung W, et al. Ephexin1 is required for structural maturation and neurotransmission at the neuromuscular junction. Neuron. 2010;65:204-16 pubmed publisher
    ..Taken together, our findings reveal an indispensible role for ephexin1 in regulating the structural maturation and neurotransmission of NMJs. ..
  18. Yang Q, Bermingham N, Finegold M, Zoghbi H. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science. 2001;294:2155-8 pubmed
    ..The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment...
  19. Fu A, Ip F, Fu W, Cheung J, Wang J, Yung W, et al. Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc Natl Acad Sci U S A. 2005;102:15224-9 pubmed
    ..Taken together, our findings reveal the essential role of Cdk5 in regulating the development of motor axons and neuromuscular synapses in vivo. ..
  20. Yang X, Li W, Prescott E, Burden S, Wang J. DNA topoisomerase IIbeta and neural development. Science. 2000;287:131-4 pubmed
    ..The defects in motor axon growth in IIbeta mutant mice resulted in a breathing impairment and death of the pups shortly after birth...
  21. Chen F, Qian L, Yang Z, Huang Y, Ngo S, Ruan N, et al. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Neuron. 2007;55:247-60 pubmed
    ..These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity. ..
  22. McMahon H, Bolshakov V, Janz R, Hammer R, Siegelbaum S, Sudhof T. Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release. Proc Natl Acad Sci U S A. 1996;93:4760-4 pubmed
    b>Synaptophysin (syp I) is a synaptic vesicle membrane protein that constitutes approximately 7% of the total vesicle protein. Multiple lines of evidence implicate syp I in a number of nerve terminal functions...
  23. Kim N, Burden S. MuSK controls where motor axons grow and form synapses. Nat Neurosci. 2008;11:19-27 pubmed
  24. Lynn F, Skewes Cox P, Kosaka Y, McManus M, Harfe B, German M. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56:2938-45 pubmed
    ..The expression of a unique profile of miRNAs is required during pancreas development and is necessary for beta-cell formation. ..
  25. Lin W, Dominguez B, Yang J, Aryal P, Brandon E, Gage F, et al. Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism. Neuron. 2005;46:569-79 pubmed
    ..Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism. ..
  26. Haase G, Dessaud E, Garces A, de Bovis B, Birling M, Filippi P, et al. GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools. Neuron. 2002;35:893-905 pubmed
    ..Thus, GDNF acts as a peripheral signal to induce PEA3 expression in specific motor neuron pools thereby regulating both cell body position and muscle innervation. ..
  27. Banks G, Chau T, Bartlett S, Noakes P. Promotion of motoneuron survival and branching in rapsyn-deficient mice. J Comp Neurol. 2001;429:156-65 pubmed
    ..Moreover, these results support the idea that skeletal muscle activity through effective synaptic transmission and intramuscular axonal branching are major mechanisms that regulate motoneuron survival during development. ..
  28. Piacentini R, Li Puma D, Ripoli C, Marcocci M, De Chiara G, Garaci E, et al. Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation. Sci Rep. 2015;5:15444 pubmed publisher
    ..neurons also exhibited: i) significantly reduced expression of the presynaptic proteins synapsin-1 and synaptophysin; ii) depressed synaptic transmission...
  29. Cheng X, Yang Y, Zhou W, Zhang Y. Expression of VGLUTs contributes to degeneration and acquisition of learning and memory. Neurobiol Learn Mem. 2011;95:361-75 pubmed publisher
    ..The expression of VGLUTs and synaptophysin (Syp) mRNA and protein in the cerebral cortex and hippocampus were investigated with real-time fluorescence ..
  30. Boettger T, Rust M, Maier H, Seidenbecher T, Schweizer M, Keating D, et al. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J. 2003;22:5422-34 pubmed
    ..These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome. ..
  31. Belfort G, Kandror K. Cellugyrin and synaptogyrin facilitate targeting of synaptophysin to a ubiquitous synaptic vesicle-sized compartment in PC12 cells. J Biol Chem. 2003;278:47971-8 pubmed
    ..domain protein that is closely related to synaptic vesicle protein synaptogyrin and, more remotely, to synaptophysin. We report here that, in PC12 cells, cellugyrin is localized in synaptic-like microvesicles (SLMVs), along ..
  32. Schilling S, Mehr A, Ludewig S, Stephan J, Zimmermann M, August A, et al. APLP1 Is a Synaptic Cell Adhesion Molecule, Supporting Maintenance of Dendritic Spines and Basal Synaptic Transmission. J Neurosci. 2017;37:5345-5365 pubmed publisher
    ..g., BACE inhibitors), those strategies may alter APP/APLP physiological function. This should be taken into account for the development of pharmaceutical treatments of Alzheimer's disease. ..
  33. Mo J, Kim C, Lee D, Sun W, Lee H, Kim H. Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. J Neurochem. 2015;133:489-500 pubmed publisher
    ..Neuronal activity-dependent up-regulation of Egr-1 might lead to altered subtypes of GABAA receptors for the maintenance of homeostatic excitatory and inhibitory balance for the regulation of synaptic strength. ..
  34. Hsu L, Mallory M, Xia Y, Veinbergs I, Hashimoto M, Yoshimoto M, et al. Expression pattern of synucleins (non-Abeta component of Alzheimer's disease amyloid precursor protein/alpha-synuclein) during murine brain development. J Neurochem. 1998;71:338-44 pubmed
    ..during development, we analyzed the levels of this protein as well as the levels of another synaptic protein (synaptophysin) by ribonuclease protection assay, western blotting, and immunocytochemistry in fetal, juvenile, and adult ..
  35. Yang J, Dominguez B, De Winter F, Gould T, Eriksson J, Lee K. Nestin negatively regulates postsynaptic differentiation of the neuromuscular synapse. Nat Neurosci. 2011;14:324-30 pubmed publisher
    ..These results suggest that nestin is required for ACh-induced, Cdk5-dependent dispersion of AChR clusters during NMJ development. ..
  36. Ohsawa S, Hamada S, Kuida K, Yoshida H, Igaki T, Miura M. Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity. Proc Natl Acad Sci U S A. 2010;107:13366-71 pubmed publisher
    ..Our findings suggest that Apaf-1/caspase-9-mediated nonapoptotic caspase signaling is required for the proper neural network formation during olfactory development. ..
  37. Yao J, Nowack A, Kensel Hammes P, Gardner R, Bajjalieh S. Cotrafficking of SV2 and synaptotagmin at the synapse. J Neurosci. 2010;30:5569-78 pubmed publisher
  38. Gitler D, Xu Y, Kao H, Lin D, Lim S, Feng J, et al. Molecular determinants of synapsin targeting to presynaptic terminals. J Neurosci. 2004;24:3711-20 pubmed
    ..Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals. ..
  39. Charnay Y, Imhof A, Vallet P, Hakkoum D, Lathuiliere A, Poku N, et al. Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience. 2008;155:714-24 pubmed publisher
    ..Although the lack of this protein does not significantly alter basic aspects of the CNS development, it may have a negative impact on neuronal development in certain motor nuclei. ..
  40. Glyvuk N, Tsytsyura Y, Geumann C, D Hooge R, Hüve J, Kratzke M, et al. AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory. EMBO J. 2010;29:1318-30 pubmed publisher
    ..The sigma1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. ..
  41. Di Paolo G, Sankaranarayanan S, Wenk M, Daniell L, Perucco E, Caldarone B, et al. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron. 2002;33:789-804 pubmed
    ..These defects correlate with increased mortality due to rare irreversible seizures and with major learning deficits, suggesting a critical role of amphiphysin for higher brain functions. ..
  42. Chen J, Billings S, Nishimune H. Calcium channels link the muscle-derived synapse organizer laminin ?2 to Bassoon and CAST/Erc2 to organize presynaptic active zones. J Neurosci. 2011;31:512-25 pubmed publisher
    ..These results suggest that presynaptic VDCCs link the target-derived synapse organizer laminin ?2 to active-zone proteins and function as scaffolding proteins to anchor active-zone proteins to the presynaptic membrane. ..
  43. Croizier S, Prevot V, Bouret S. Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life. Cell Rep. 2016;15:36-44 pubmed publisher
  44. Wang L, Nomura M, Goto Y, Tanaka K, Sakamoto R, Abe I, et al. Smad2 protein disruption in the central nervous system leads to aberrant cerebellar development and early postnatal ataxia in mice. J Biol Chem. 2011;286:18766-74 pubmed publisher
    ..These findings indicate that Smad2 plays a key role in cerebellar development and motor function control. ..
  45. Li X, Dong X, Luo S, Zhang B, Lee D, Ting A, et al. Retrograde regulation of motoneuron differentiation by muscle beta-catenin. Nat Neurosci. 2008;11:262-8 pubmed publisher
    ..Taken together, these observations indicate a role for muscle beta-catenin in presynaptic differentiation and function, identifying a previously unknown retrograde signaling in the synapse formation and synaptic plasticity. ..
  46. Ventruti A, Kazdoba T, Niu S, D ARCANGELO G. Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience. 2011;189:32-42 pubmed publisher
    ..These studies may provide insights into the etiology of cognitive disorders associated with deficiencies in Reelin signaling and PTEN dysfunction. ..
  47. Guedj F, Pereira P, Najas S, Barallobre M, Chabert C, Souchet B, et al. DYRK1A: a master regulatory protein controlling brain growth. Neurobiol Dis. 2012;46:190-203 pubmed publisher
    ..In addition, six genes involved either in cell division (Ccnd1 and pAkt) or in neuronal machinery (Gap43, Map2, Syp, Snap25) were regulated by Dyrk1a throughout development, from birth to adult...
  48. Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger B, Ichida J, et al. CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature. 2013;495:474-80 pubmed publisher
    ..Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53. ..
  49. Takayama C, Inoue Y. Developmental localization of potassium chloride co-transporter 2 (KCC2) in the Purkinje cells of embryonic mouse cerebellum. Neurosci Res. 2007;57:322-5 pubmed
    ..These results suggest that GABA might become inhibitory on the Purkinje cells after their settling in the Purkinje cell layer. ..
  50. Messéant J, Dobbertin A, Girard E, Delers P, Manuel M, Mangione F, et al. MuSK frizzled-like domain is critical for mammalian neuromuscular junction formation and maintenance. J Neurosci. 2015;35:4926-41 pubmed publisher
    ..Together, our data reveal that MuSK CRD is critical for NMJ formation and plays an unsuspected role in NMJ maintenance in adulthood. ..
  51. Harmon E, Apelqvist A, Smart N, Gu X, Osborne D, Kim S. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Development. 2004;131:6163-74 pubmed
    ..Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development. ..
  52. Puig I, Champeval D, de Santa Barbara P, Jaubert F, Lyonnet S, Larue L. Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction. J Clin Invest. 2009;119:3586-96 pubmed publisher
    ..Our study thus reveals that loss of PTEN disrupts development of the ENS and identifies the PI3K/PTEN-AKT-S6K signaling pathway as a potential therapeutic target for ganglioneuromatosis forms of CIPO. ..
  53. Saito K, Kakizaki T, Hayashi R, Nishimaru H, Furukawa T, Nakazato Y, et al. The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice. Mol Brain. 2010;3:40 pubmed publisher
    ..VGAT knockout mice will be useful for further investigating the roles of VGAT in normal physiology and pathophysiologic processes. ..