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PMID: 20434989 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines.

Cell ·Vol. 141 ·No. 3 ·2010-04-30 ·Pages 524-35

Kennedy MJ, Davison IG, Robinson CG, Ehlers MD

Abstract

Changes in postsynaptic membrane composition underlie many forms of learning-related synaptic plasticity in the brain. At excitatory glutamatergic synapses, fusion of intracellular vesicles at or near the postsynaptic plasma membrane is critical for dendritic spine morphology, retrograde synaptic signaling, and long-term synaptic plasticity. Whereas the molecular machinery for exocytosis in presynaptic terminals has been defined in detail, little is known about the location, kinetics, regulation, or molecules involved in postsynaptic exocytosis. Here, we show that an exocytic domain adjacent to the postsynaptic density (PSD) enables fusion of large, AMPA receptor-containing recycling compartments during elevated synaptic activity. Exocytosis occurs at microdomains enriched in the plasma membrane t-SNARE syntaxin 4 (Stx4), and disruption of Stx4 impairs both spine exocytosis and long-term potentiation (LTP) at hippocampal synapses. Thus, Stx4 defines an exocytic zone that directs membrane fusion for postsynaptic plasticity, revealing a novel specialization for local membrane traffic in dendritic spines.

MeSH Terms
Animals Cell Membrane/metabolism Cells, Cultured Dendritic Spines/metabolism Endosomes/metabolism Exocytosis Gene Knockdown Techniques Hippocampus/cytology,metabolism Humans Mice Mice, Inbred C57BL Qa-SNARE Proteins/genetics,metabolism Rats SNARE Proteins/metabolism
Chemicals
Qa-SNARE Proteins SNARE Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kennedy Matthew J
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Davison Ian G
Robinson Camenzind G
Ehlers Michael D
References (46)
46 references, click to expand
  1. Role of AMPA receptor cycling in synaptic transmission and plasticity.
    Neuron. 1999 Nov;24(3):649-58 PMID: 10595516
  2. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins.
    Nature. 1998 Jul 9;394(6689):192-5 PMID: 9671304
  3. Site of docking and fusion of insulin secretory granules in live MIN6 beta cells analyzed by TAT-conjugated anti-syntaxin 1 antibody and total internal reflection fluorescence microscopy.
    J Biol Chem. 2004 Feb 27;279(9):8403-8 PMID: 14676208
  4. Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity.
    Cell. 2008 Oct 31;135(3):535-48 PMID: 18984164
  5. Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines.
    Neuron. 2002 Oct 24;36(3):435-49 PMID: 12408846
  6. All-or-none potentiation at CA3-CA1 synapses.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4732-7 PMID: 9539807
  7. Organelles and trafficking machinery for postsynaptic plasticity.
    Annu Rev Neurosci. 2006;29:325-62 PMID: 16776589
  8. Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes.
    Neuron. 2006 Dec 7;52(5):817-30 PMID: 17145503
  9. Mechanisms of membrane fusion: disparate players and common principles.
    Nat Rev Mol Cell Biol. 2008 Jul;9(7):543-56 PMID: 18496517
  10. The SNARE motif is essential for the formation of syntaxin clusters in the plasma membrane.
    Biophys J. 2006 Apr 15;90(8):2843-51 PMID: 16443657
  11. Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons.
    Neuron. 2001 Jan;29(1):243-54 PMID: 11182095
  12. Glutamate receptor dynamics in dendritic microdomains.
    Neuron. 2008 May 22;58(4):472-97 PMID: 18498731
  13. SNAREs--engines for membrane fusion.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43 PMID: 16912714
  14. Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane.
    EMBO J. 2006 Apr 19;25(8):1623-34 PMID: 16601687
  15. Spine expansion and stabilization associated with long-term potentiation.
    J Neurosci. 2008 May 28;28(22):5740-51 PMID: 18509035
  16. Long-term potentiation of exogenous glutamate responses at single dendritic spines.
    Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14434-9 PMID: 16186507
  17. AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis.
    Neuron. 2009 Nov 12;64(3):381-90 PMID: 19914186
  18. Lateral organization of endocytic machinery in dendritic spines.
    Nat Neurosci. 2004 Sep;7(9):917-8 PMID: 15322548
  19. SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis.
    EMBO J. 2001 May 1;20(9):2202-13 PMID: 11331586
  20. New concepts in synaptic biology derived from single-molecule imaging.
    Neuron. 2008 Aug 14;59(3):359-74 PMID: 18701063
  21. Photoinactivation of native AMPA receptors reveals their real-time trafficking.
    Neuron. 2005 Dec 22;48(6):977-85 PMID: 16364901
  22. Structural basis of long-term potentiation in single dendritic spines.
    Nature. 2004 Jun 17;429(6993):761-6 PMID: 15190253
  23. Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation.
    Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11388-93 PMID: 18682558
  24. Calcium-evoked dendritic exocytosis in cultured hippocampal neurons. Part I: trans-Golgi network-derived organelles undergo regulated exocytosis.
    J Neurosci. 1998 Sep 1;18(17):6803-13 PMID: 9712651
  25. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines.
    Science. 2008 Mar 21;319(5870):1683-7 PMID: 18309046
  26. Anatomy and dynamics of a supramolecular membrane protein cluster.
    Science. 2007 Aug 24;317(5841):1072-6 PMID: 17717182
  27. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons.
    Nat Neurosci. 2001 Sep;4(9):917-26 PMID: 11528423
  28. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion.
    Cell. 1993 Nov 5;75(3):409-18 PMID: 8221884
  29. The cell biology of synaptic plasticity: AMPA receptor trafficking.
    Annu Rev Cell Dev Biol. 2007;23:613-43 PMID: 17506699
  30. Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology.
    J Neurosci. 2006 Jun 28;26(26):7046-55 PMID: 16807334
  31. Real-time imaging of discrete exocytic events mediating surface delivery of AMPA receptors.
    J Neurosci. 2007 Oct 10;27(41):11112-21 PMID: 17928453
  32. Syntaxins 3 and 4 are concentrated in separate clusters on the plasma membrane before the establishment of cell polarity.
    Mol Biol Cell. 2006 Feb;17(2):977-89 PMID: 16339081
  33. Graded bidirectional synaptic plasticity is composed of switch-like unitary events.
    Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9679-84 PMID: 15983385
  34. Postsynaptic membrane fusion and long-term potentiation.
    Science. 1998 Jan 16;279(5349):399-403 PMID: 9430593
  35. Endocytic trafficking and recycling maintain a pool of mobile surface AMPA receptors required for synaptic potentiation.
    Neuron. 2009 Jul 16;63(1):92-105 PMID: 19607795
  36. GluR1 links structural and functional plasticity at excitatory synapses.
    J Neurosci. 2007 Dec 12;27(50):13706-18 PMID: 18077682
  37. Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer.
    Neuron. 2007 Sep 20;55(6):874-89 PMID: 17880892
  38. Filamentous actin regulates insulin exocytosis through direct interaction with Syntaxin 4.
    J Biol Chem. 2008 Apr 18;283(16):10716-26 PMID: 18285343
  39. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release.
    Nat Neurosci. 2009 Jun;12(6):767-76 PMID: 19448629
  40. Syntaxin 4, VAMP2, and/or VAMP3/cellubrevin are functional target membrane and vesicle SNAP receptors for insulin-stimulated GLUT4 translocation in adipocytes.
    Mol Cell Biol. 1997 May;17(5):2425-35 PMID: 9111311
  41. Molecular anatomy of a trafficking organelle.
    Cell. 2006 Nov 17;127(4):831-46 PMID: 17110340
  42. Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation.
    J Neurosci. 2006 Feb 15;26(7):2000-9 PMID: 16481433
  43. Recycling endosomes supply AMPA receptors for LTP.
    Science. 2004 Sep 24;305(5692):1972-5 PMID: 15448273
  44. Modeling synaptic dynamics driven by receptor lateral diffusion.
    Biophys J. 2006 Oct 1;91(7):2405-15 PMID: 16844759
  45. Retrograde signaling by Syt 4 induces presynaptic release and synapse-specific growth.
    Science. 2005 Nov 4;310(5749):858-63 PMID: 16272123
  46. Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting.
    Neuron. 2000 Nov;28(2):511-25 PMID: 11144360
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.02.042
Published
2010-04-30
Pages
524-35
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2874581
Subset
IM
Grants
NIA NIH HHS · R01 AG024492 · United States
NINDS NIH HHS · R01 NS047574 · United States
NINDS NIH HHS · R01 NS047574-05 · United States
NIMH NIH HHS · R01 MH064748 · United States
NIMH NIH HHS · R01 MH064748-05 · United States
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH064748-03 · United States
NIMH NIH HHS · R01 MH064748-04 · United States
NINDS NIH HHS · R01 NS047574-06 · United States
NINDS NIH HHS · R01 NS047574-07 · United States
NIA NIH HHS · R01 AG024492-05 · United States
Corrections
CommentIn
PMID: 20814225
External Links
PubMed source DOI: 10.1016/j.cell.2010.02.042 PMC Full Text View journal details
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