Research Topics
| Michael EhlersSummaryAffiliation: Duke University Medical Center Country: USA Publications
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Publications
Synapse structure: glutamate receptors connected by the shanksM D Ehlers
Department of Neurobiology, Duke University Medical Center, Durham, 27710, USA
Curr Biol 9:R848-50. 1999..A family of proteins has been identified whose members, the Shanks, physically link two major receptor complexes at excitatory synapses - NMDA receptors and metabotropic glutamate receptors...
Dendrite development: a surprising originMichael D Ehlers
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
J Cell Biol 170:517-9. 2005..Neurons extend elaborate dendrites studded with spines. Unexpectedly, this cellular sculpting is regulated by the origin recognition complex -- the core machinery for initiating DNA replication...
Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomesMikyoung Park
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Neuron 52:817-30. 2006....
Secrets of the secretory pathway in dendrite growthMichael D Ehlers
Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neuron 55:686-9. 2007..Dendrites and axons exhibit different morphologies and patterns of growth. This difference in neuronal structure is controlled by evolutionarily conserved directed trafficking through the secretory pathway...
Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activityMichael D Ehlers
Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
Neuron 54:447-60. 2007..Thus, local activity restricts GluR1 mobility on a submicron scale, defining an input-specific mechanism for regulating AMPA receptor composition and abundance...
Synapse formation: astrocytes spout offMichael D Ehlers
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Curr Biol 15:R134-7. 2005..Trillions of synapses form as the brain develops. This intimate contact between two neurons has now been shown to be facilitated by thrombospondins - large extracellular matrix proteins secreted by astrocytes...
Eppendorf 2003 prize-winning essay. Ubiquitin and the deconstruction of synapsesMichael D Ehlers
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Science 302:800-1. 2003
Deconstructing the axon: Wallerian degeneration and the ubiquitin-proteasome systemMichael D Ehlers
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Trends Neurosci 27:3-6. 2004
Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome systemMichael D Ehlers
Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA
Nat Neurosci 6:231-42. 2003....
Molecular morphogens for dendritic spinesMichael D Ehlers
Dept of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Trends Neurosci 25:64-7. 2002..These new studies reveal linkages between receptor complexes, the actin cytoskeleton and signaling molecules that help shape spines...
Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sortingM D Ehlers
Department of Neurobiology, Duke University Medical Center, Durham 27710, USA
Neuron 28:511-25. 2000..These results demonstrate that activity regulates AMPAR endocytic sorting, providing a potential mechanistic link between rapid and chronic changes in synaptic strength...
Ubiquitin and synaptic dysfunction: ataxic mice highlight new common themes in neurological diseaseMichael D Ehlers
Departments of Neurobiology, Cell Biology and Pharmacology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Trends Neurosci 26:4-7. 2003
Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptorsYuanyue Mu
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Neuron 40:581-94. 2003....
Metaplasticity at single glutamatergic synapsesMing Chia Lee
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neuron 66:859-70. 2010..Thus, spontaneous glutamate release adjusts plasticity threshold at single synapses by local regulation of NMDA receptors, providing a novel spatially delimited form of synaptic metaplasticity...
Neurabin/protein phosphatase-1 complex regulates dendritic spine morphogenesis and maturationRyan T Terry-Lorenzo
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
Mol Biol Cell 16:2349-62. 2005....
Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1Isabel Pérez-Otaño
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, North Carolina 27710, USA
Nat Neurosci 9:611-21. 2006....
Dual modes of endoplasmic reticulum-to-Golgi transport in dendrites revealed by live-cell imagingApril C Horton
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
J Neurosci 23:6188-99. 2003..This distributed dendritic Golgi represents an organization of the secretory pathway unique among mammalian cells...
Pruning and loss of excitatory synapses by the parkin ubiquitin ligaseThomas D Helton
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Proc Natl Acad Sci U S A 105:19492-7. 2008..Thus, parkin negatively regulates the number and strength of excitatory synapses. Increased excitatory drive produced by disruption of parkin may contribute to the pathophysiology of PD...
Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spinesThomas A Blanpied
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neuron 36:435-49. 2002..These results reveal the presence of a novel specialization dedicated to endocytosis near the postsynaptic membrane...
Recycling endosomes supply AMPA receptors for LTPMikyoung Park
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Science 305:1972-5. 2004..Thus, recycling endosomes supply AMPA receptors for LTP and provide a mechanistic link between synaptic potentiation and membrane remodeling during synapse modification...
Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesisApril C Horton
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Neuron 48:757-71. 2005..These results define a novel polarized organization of neuronal secretory trafficking and demonstrate a mechanistic link between directed membrane trafficking and asymmetric dendrite growth...
Structural plasticity with preserved topology in the postsynaptic protein networkThomas A Blanpied
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Proc Natl Acad Sci U S A 105:12587-92. 2008..We propose a flexible matrix model of the PSD based on stable molecular positioning of PSD-95 scaffolds...
Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological diseaseThomas A Blanpied
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Biol Psychiatry 55:1121-7. 2004....
Endocytosis and degradative sorting of NMDA receptors by conserved membrane-proximal signalsDerek B Scott
Program in Cell and Molecular Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
J Neurosci 24:7096-109. 2004..These results define a novel conserved signature of NMDARs regulating internalization and postendocytic trafficking...
Secretory trafficking in neuronal dendritesApril C Horton
Department of Neurobiology, Duke University Medical Center, Box 3209 Durham, NC 27710, USA
Nat Cell Biol 6:585-91. 2004....
Secretory outposts for the local processing of membrane cargo in neuronal dendritesCyril Hanus
Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
Traffic 9:1437-45. 2008..Here we review what is currently known about dendritic secretory organelles and their role in the development, maintenance and plasticity of postsynaptic compartments...
Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticityZhiping Wang
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
Cell 135:535-48. 2008..Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity...
Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamicsNatan T Shaked
1Department of Biomedical Engineering, Fitzpatrick Institute for Photonics, Duke University, Durham, North Carolina 27708, USA
Appl Opt 49:2872-8. 2010..The method is demonstrated experimentally through phase microscopy of neurons and unicellular microorganisms...
Ubiquitin and protein turnover in synapse functionJason J Yi
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, North Carolina 27710, USA
Neuron 47:629-32. 2005..These recent findings raise intriguing questions as to how enduring changes at synapses are accomplished in the face of robust, ongoing molecular turnover...
Organelles and trafficking machinery for postsynaptic plasticityMatthew J Kennedy
Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Annu Rev Neurosci 29:325-62. 2006....
Learning from NMDA receptor trafficking: clues to the development and maturation of glutamatergic synapsesIsabel Pérez-Otaño
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, N C 27710, USA
Neurosignals 13:175-89. 2004..Here, we review recent evidence that challenges this view, focusing on the role that activity plays in altering NMDAR trafficking and how such dynamic regulation of NMDARs may impact on the plasticity of neural circuits...
Spine microdomains for postsynaptic signaling and plasticityThomas M Newpher
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Trends Cell Biol 19:218-27. 2009..We discuss the emerging functions of glutamate receptors residing within sub-spine microdomains and propose a model for distinct signaling platforms with specialized functions in synaptic plasticity...
Neuronal polarity and traffickingApril C Horton
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA
Neuron 40:277-95. 2003....
Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neuronsDhanrajan M Tiruchinapalli
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
RNA Biol 5:157-68. 2008..We propose that post-transcriptional regulation of neuronal mRNAs by HuD RBPs mediates protein synthesis-dependent changes in synaptic plasticity...
Age-related regulation of dendritic endocytosis associated with altered clathrin dynamicsThomas A Blanpied
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neurobiol Aging 24:1095-104. 2003..Thus, endocytic function in dendrites is altered in older neurons, suggesting that as neurons age, protein trafficking mechanisms are controlled to complement maturational requirements...
Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to HomerJiuyi Lu
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neuron 55:874-89. 2007..Thus, a physical link between the PSD and the EZ ensures localized endocytosis and recycling by recapturing and maintaining a proximate pool of cycling AMPA receptors...
Emerging roles for ubiquitin and protein degradation in neuronal functionJason J Yi
Program in Cell and Molecular Biology, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
Pharmacol Rev 59:14-39. 2007..Here, we summarize existing knowledge about the role of the UPS in brain function, highlighting recent work delineating its importance in neuronal development, plasticity, and degeneration...
Cell type-specific dendritic polarity in the absence of spatially organized external cuesApril C Horton
Department of Neurobiology, Durham, NC, 27710, USA
Brain Cell Biol 35:29-38. 2006..Thus, pyramidal neurons have a cellular program for polarized dendrite growth independent of tissue microenvironment...
Genetic control of neuronal activity in mice conditionally expressing TRPV1Benjamin R Arenkiel
Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, North Carolina 27710, USA
Nat Methods 5:299-302. 2008..Application of the TRPV1 ligand capsaicin induced strong inward currents, triggered action potentials and activated stereotyped behaviors, allowing cell type-specific chemical genetic control of neuronal activity in vitro and in vivo...
Ubiquitination in postsynaptic function and plasticityAngela M Mabb
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Annu Rev Cell Dev Biol 26:179-210. 2010..We describe postsynaptic ubiquitination pathways and their role in brain development, neuronal physiology, and brain disorders...
TGF-beta signaling specifies axons during brain developmentJason J Yi
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Cell 142:144-57. 2010..These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain...
Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptorsDerek B Scott
Program in Cell and Molecular Biology, Duke University Medical Center, Durham, NC 27710, USA
Neuropharmacology 45:755-67. 2003....
Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spinesMatthew J Kennedy
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Cell 141:524-35. 2010..Thus, Stx4 defines an exocytic zone that directs membrane fusion for postsynaptic plasticity, revealing a novel specialization for local membrane traffic in dendritic spines...
Molecular genetics and imaging technologies for circuit-based neuroanatomyBenjamin R Arenkiel
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, North Carolina 27710, USA
Nature 461:900-7. 2009..This sophisticated molecular and genetic 'toolbox', coupled with new methods in optical and electron microscopy, provides an expanding array of techniques for probing neural anatomy and function...
In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2Benjamin R Arenkiel
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
Neuron 54:205-18. 2007....
Glutamate receptor dynamics in dendritic microdomainsThomas M Newpher
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Neuron 58:472-97. 2008..We also examine the cooperative relationship between intracellular trafficking and surface diffusion of glutamate receptors that underlies the expression of learning-related synaptic plasticity...
Apolipoprotein E receptor 2 interactions with the N-methyl-D-aspartate receptorHYANG SOOK HOE
Department of Neuroscience and Physiology, Georgetown University Medical Center, Washington, DC 20057 1464, USA
J Biol Chem 281:3425-31. 2006..These studies suggest that ApoEr2 can form a multiprotein complex with NMDA receptor subunits and PSD95...
Lateral organization of endocytic machinery in dendritic spinesBence Racz
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Nat Neurosci 7:917-8. 2004..Thus, previously unrecognized lateral domains of the spine organize endocytic protein machinery at sites removed from the postsynaptic density...
Homeostatic plasticity and NMDA receptor traffickingIsabel Pérez-Otaño
Department of Neurosciences, CIMA, University of Navarra Medical School, Pamplona, 31008, Spain
Trends Neurosci 28:229-38. 2005..An emerging concept is that activity-dependent alterations in NMDA receptor trafficking contribute to homeostatic plasticity at central glutamatergic synapses...
Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actininIoannis E Michailidis
Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA
J Neurosci 27:5523-32. 2007..Thus, our results extend the influence of PIP2 to the NMDA ionotropic glutamate receptors and introduce a novel mechanism of "indirect" regulation of transmembrane protein activity by PIP2...
Research Grants
- Molecular Targets of A-beta-Induced Synaptic DysfunctionMichael Ehlers; Fiscal Year: 2007..As such, the proposed research holds promise for the development of new therapeutic approaches for AD-associated memory loss and cognitive deficit. ..
- The Endocytic Machinery of Dendritic SpinesMichael Ehlers; Fiscal Year: 2007..abstract_text> ..
- Synaptic Targeting of NMDA ReceptorsMichael Ehlers; Fiscal Year: 2009..Moreover, because NMDA receptors participate in the pathogenesis of a wide range of neurologic disorders, psychiatric disease, and states of addiction, these studies hold promise for the development of novel therapeutic strategies. ..
- The Endocytic Machinery of Dendritic SpinesMichael Ehlers; Fiscal Year: 2009....
- The Endocytic Machinery of Dendritic SpinesMichael D Ehlers; Fiscal Year: 2010....
- Intracellular Trafficking of AMPA ReceptorsMichael Ehlers; Fiscal Year: 2006....
- SYNAPTIC TARGETING AND CLUSTERING AND NMDA RECEPTORSMichael Ehlers; Fiscal Year: 2004..Together, the proposed experiments will elucidate basic molecular mechanisms underlying synaptic transmission and synaptic plasticity. ..
- Non-invasive Chemical Genetic Control of Neuronal ActivityMichael D Ehlers; Fiscal Year: 2010....
