title: Differential targeting of dynamin-1 and dynamin-3 to nerve terminals during chronic suppression of neuronal activity.
abstract: Neurons express three closely related dynamin genes. Dynamin 1 has long been implicated in the regulation of synaptic vesicle recycling in nerve terminals, and dynamins 2 and 3 were more recently shown also to contribute to synaptic vesicle recycling in specific and distinguishable ways. In cultured hippocampal neurons we found that chronic suppression of spontaneous network activity differentially regulated the targeting of endogenous dynamins 1 and 3 to nerve terminals, while dynamin 2 was unaffected. Specifically, when neural activity was chronically silenced for 1-2weeks by tetrodotoxin (TTX), the clustering of dynamin 1 at nerve terminals was reduced, while the clustering of dynamin 3 significantly increased. Moreover, dynamin 3 clustering was induced within hours by the sustained blockade of AMPA receptors, suggesting that AMPA receptors may function to prevent Dyn3 accumulation within nerve terminals. Clustering of dynamin 3 was induced by an antagonist of the calcium-dependent protein phosphatase calcineurin, but was not dependent upon intact actin filaments. TTX-induced clustering of Dyn3 occurred with a markedly slower time-course than the previously described clustering of synapsin 1. Potassium-induced depolarization rapidly de-clustered dynamin 3 from nerve terminals within minutes. These results, which have implications for homeostatic synapse restructuring, indicate that the three dynamins have evolved different regulatory mechanisms for trafficking to and from nerve terminals in response to changes in neural activity.
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA, United States; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA, United States. Electronic address: bcalabrese@ucsd.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Calabrese
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA, United States; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA, United States. Electronic address: shalpain@ucsd.edu.
authors.forename: Shelley
authors.initials: S
authors.lastname: Halpain
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism*; D034286:Dynamin III / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007166:Immunosuppressive Agents; D011810:Quinoxalines; D026941:Sodium Channel Blockers; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; C056723:FG 9041; C058028:immunomycin; D034284:Dynamin I; D034286:Dynamin III; D016559:Tacrolimus
keywords: Calcineurin; Endocytosis; Homeostatic plasticity; Membrane trafficking; Synaptic vesicle; Tetrodotoxin
references.citation: Nat Rev Mol Cell Biol. 2003 Feb;4(2):127-39
references.pmid: 12563290
references.citation: Prog Neurobiol. 2010 Aug;91(4):313-48
references.pmid: 20438797
references.citation: Front Cell Neurosci. 2013 Nov 21;7:223
references.pmid: 24312013
references.citation: Curr Biol. 1998 Jun 18;8(13):740-9
references.pmid: 9651678
references.citation: Biochem Soc Symp. 2005;(72):87-97
references.pmid: 15649133
references.citation: Science. 2007 Apr 27;316(5824):570-4
references.pmid: 17463283
references.citation: Curr Opin Neurobiol. 1997 Jun;7(3):323-30
references.pmid: 9232811
references.citation: Neuron. 1998 Nov;21(5):1067-78
references.pmid: 9856462
references.citation: J Neurophysiol. 2012 Jun;107(12):3479-92
references.pmid: 22457456
references.citation: J Neurochem. 1992 Oct;59(4):1336-43
references.pmid: 1328520
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10817-22
references.pmid: 19509338
references.citation: J Neurochem. 1996 Sep;67(3):927-31
references.pmid: 8752097
references.citation: J Neurochem. 2011 Apr;117(1):48-60
references.pmid: 21210813
references.citation: Curr Biol. 2003 Mar 18;13(6):510-5
references.pmid: 12646135
references.citation: Mol Biol Cell. 2008 Dec;19(12):5347-59
references.pmid: 18923138
references.citation: Trends Cell Biol. 1999 Mar;9(3):96-102
references.pmid: 10201074
references.citation: Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8376-80
references.pmid: 1387713
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):377-84
references.pmid: 9012790
references.citation: Prog Neurobiol. 2006 Nov;80(4):177-217
references.pmid: 17074429
references.citation: Neuroscience. 1993 Jul;55(1):113-27
references.pmid: 8350983
references.citation: J Biol Chem. 1997 Dec 5;272(49):30984-92
references.pmid: 9388246
references.citation: Trends Neurosci. 1994 Aug;17(8):348-53
references.pmid: 7526507
references.citation: Neuron. 2011 Jun 23;70(6):1100-14
references.pmid: 21689597
references.citation: J Neurosci Res. 2002 Aug 15;69(4):427-36
references.pmid: 12210837
references.citation: Nat Rev Neurosci. 2008 May;9(5):344-56
references.pmid: 18425089
references.citation: Front Endocrinol (Lausanne). 2013 Sep 18;4:126
references.pmid: 24065954
references.citation: J Biol Chem. 2011 Sep 2;286(35):30295-303
references.pmid: 21730063
references.citation: Nat Neurosci. 2001 Dec;4(12):1187-93
references.pmid: 11685225
references.citation: Biochim Biophys Acta. 2011 Oct;1813(10):1689-99
references.pmid: 21195118
references.citation: Mol Biol Cell. 1998 Sep;9(9):2595-609
references.pmid: 9725914
references.citation: Nat Cell Biol. 2003 Aug;5(8):701-10
references.pmid: 12855954
references.citation: Nat Rev Mol Cell Biol. 2012 Feb;13(2):75-88
references.pmid: 22233676
references.citation: Science. 1994 Aug 12;265(5174):970-3
references.pmid: 8052858
references.citation: Cell Adh Migr. 2013 Jul-Aug;7(4):379-87
references.pmid: 23628914
references.citation: J Neurosci. 2004 Feb 25;24(8):2004-12
references.pmid: 14985443
references.citation: J Biol Chem. 1994 Dec 2;269(48):30132-9
references.pmid: 7982917
references.citation: J Biol Chem. 2007 May 18;282(20):14695-707
references.pmid: 17376771
references.citation: J Neurosci. 2005 Nov 23;25(47):10913-21
references.pmid: 16306404
references.citation: Neuron. 2010 May 13;66(3):337-51
references.pmid: 20471348
references.citation: Cell Struct Funct. 2011;36(2):145-54
references.pmid: 21150131
references.citation: J Neurosci. 2014 May 21;34(21):7266-80
references.pmid: 24849359
references.citation: J Cell Biol. 2014 Mar 3;204(5):759-75
references.pmid: 24590174
references.citation: Neuron. 2006 Jul 20;51(2):179-86
references.pmid: 16846853
references.citation: Trends Neurosci. 2001 Nov;24(11):659-65
references.pmid: 11672811
references.citation: Neuron. 2007 Sep 20;55(6):874-89
references.pmid: 17880892
references.citation: Biochem Soc Trans. 2009 Oct;37(Pt 5):1022-6
references.pmid: 19754444
references.citation: Physiology (Bethesda). 2006 Feb;21:38-47
references.pmid: 16443821
references.citation: Nature. 1998 Feb 26;391(6670):892-6
references.pmid: 9495341
references.citation: J Cell Sci. 2005 Mar 15;118(Pt 6):1279-90
references.pmid: 15741233
references.citation: J Biol Chem. 2013 Jun 28;288(26):19050-9
references.pmid: 23687302
references.citation: Annu Rev Cell Dev Biol. 2009;25:133-60
references.pmid: 19575674