title: Protein kinase C is a calcium sensor for presynaptic short-term plasticity.
abstract: In presynaptic boutons, calcium (Ca(2+)) triggers both neurotransmitter release and short-term synaptic plasticity. Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca(2+) to their C2 domains, the proteins that sense smaller global Ca(2+) increases to produce short-term plasticity have remained elusive. Here, we identify a Ca(2+) sensor for post-tetanic potentiation (PTP), a form of plasticity thought to underlie short-term memory. We find that at the functionally mature calyx of Held synapse the Ca(2+)-dependent protein kinase C isoforms α and β are necessary for PTP, and the expression of PKCβ in PKCαβ double knockout mice rescues PTP. Disruption of Ca(2+) binding to the PKCβ C2 domain specifically prevents PTP without impairing other PKCβ-dependent forms of synaptic enhancement. We conclude that different C2-domain-containing presynaptic proteins are engaged by different Ca(2+) signals, and that Ca(2+) increases evoked by tetanic stimulation are sensed by PKCβ to produce PTP.DOI: http://dx.doi.org/10.7554/eLife.03011.001.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, United States Center for Neuroscience, University of California, Davis, Davis, United States.
authors.forename: Diasynou
authors.initials: D
authors.lastname: Fioravante
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: YunXiang
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Arthur Ph
authors.initials: AP
authors.lastname: de Jong
authors.affiliation: The Biotechnology Center of Oslo, University of Oslo, Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Pascal S
authors.initials: PS
authors.lastname: Kaeser
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, United States wade_regehr@hms.harvard.edu.
authors.forename: Wade G
authors.initials: WG
authors.lastname: Regehr
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D064546:Protein Kinase C beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha
keywords: calcium; phorbol ester; post-tetanic potentiation; protein kinase C; short-term plasticity; synaptotagmin
references.citation: Curr Opin Neurobiol. 2011 Apr;21(2):269-74
references.pmid: 21353526
references.citation: J Neurosci. 2009 Jul 29;29(30):9510-20
references.pmid: 19641114
references.citation: Curr Biol. 1996 Nov 1;6(11):1509-18
references.pmid: 8939606
references.citation: Elife. 2014 Feb 11;3:e01715
references.pmid: 24520164
references.citation: J Neurosci. 2005 May 25;25(21):5127-37
references.pmid: 15917453
references.citation: Nat Neurosci. 2003 Jun;6(6):551-2
references.pmid: 12754518
references.citation: Biochemistry. 2003 Oct 14;42(40):11669-81
references.pmid: 14529277
references.citation: Neuron. 2008 Jan 24;57(2):210-6
references.pmid: 18215619
references.citation: Annu Rev Physiol. 2014;76:333-63
references.pmid: 24274737
references.citation: Cell. 2004 Aug 6;118(3):389-401
references.pmid: 15294163
references.citation: Mol Endocrinol. 2002 Apr;16(4):847-58
references.pmid: 11923480
references.citation: EMBO J. 1998 Jul 15;17(14):3921-30
references.pmid: 9670009
references.citation: Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4
references.pmid: 15380221
references.citation: Neuron. 2010 Jul 15;67(1):100-15
references.pmid: 20624595
references.citation: Neuron. 2013 Oct 30;80(3):675-90
references.pmid: 24183019
references.citation: J Physiol. 2007 Jun 1;581(Pt 2):467-78
references.pmid: 17363387
references.citation: Structure. 1998 Nov 15;6(11):1395-405
references.pmid: 9817842
references.citation: J Neurosci. 2013 Mar 13;33(11):4625-33
references.pmid: 23486937
references.citation: J Physiol. 2010 Dec 15;588(Pt 24):4987-94
references.pmid: 21041528
references.citation: Nature. 2004 Oct 14;431(7010):796-803
references.pmid: 15483601
references.citation: Biochemistry. 2001 Nov 6;40(44):13216-29
references.pmid: 11683630
references.citation: Cold Spring Harb Perspect Biol. 2012 Jan 01;4(1):a011353
references.pmid: 22068972
references.citation: J Cell Sci. 2002 Dec 1;115(Pt 23):4399-411
references.pmid: 12414987
references.citation: Neuron. 2001 Dec 20;32(6):1119-31
references.pmid: 11754842
references.citation: Biochemistry. 2001 Mar 13;40(10):3089-100
references.pmid: 11258923
references.citation: J Physiol. 2005 Apr 1;564(Pt 1):173-87
references.pmid: 15695246
references.citation: Science. 1996 Jul 12;273(5272):248-51
references.pmid: 8662510
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14017-21
references.pmid: 11717460
references.citation: Neuron. 2007 Apr 19;54(2):275-90
references.pmid: 17442248
references.citation: J Neurosci. 2012 Sep 19;32(38):13004-9
references.pmid: 22993418
references.citation: Neuron. 2011 Apr 28;70(2):244-51
references.pmid: 21521611
references.citation: Nature. 2009 May 7;459(7243):93-7
references.pmid: 19279571
references.citation: J Neurosci. 2005 Apr 20;25(16):4131-40
references.pmid: 15843616
references.citation: Curr Opin Neurobiol. 2009 Jun;19(3):245-53
references.pmid: 19559598
references.citation: Science. 1996 Aug 9;273(5276):788-91
references.pmid: 8670417
references.citation: Biochemistry. 2002 Sep 24;41(38):11411-24
references.pmid: 12234184
references.citation: Neuron. 2014 May 21;82(4):859-71
references.pmid: 24794094
references.citation: Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E395-402
references.pmid: 19934406
references.citation: Protein Sci. 1996 Dec;5(12):2375-90
references.pmid: 8976547
references.citation: Science. 2010 Mar 26;327(5973):1614-8
references.pmid: 20150444
references.citation: Neuron. 1999 Jun;23(2):399-409
references.pmid: 10399944
references.citation: J Neurosci. 1994 Feb;14(2):523-37
references.pmid: 8301352
references.citation: J Cell Biol. 2003 Jun 9;161(5):899-909
references.pmid: 12782683
references.citation: J Neurosci. 2005 Apr 13;25(15):3842-50
references.pmid: 15829636
references.citation: Nat Struct Mol Biol. 2010 Mar;17(3):280-8
references.pmid: 20154707
references.citation: Neuron. 2011 Jun 9;70(5):1005-19
references.pmid: 21658591