title: Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems.
abstract: Complexins (Cplxs) are small, SNARE-associated proteins believed to regulate fast, calcium-triggered exocytosis. However, studies have pointed to either an inhibitory and/or facilitatory role in exocytosis, and the role of Cplxs in synchronizing exocytosis is relatively unexplored. Here, we compare the function of two types of complexin, Cplx 1 and 2, in two model systems of calcium-dependent exocytosis. In mouse neuromuscular junctions (NMJs), we find that lack of Cplx 1 significantly reduces and desynchronizes calcium-triggered synaptic transmission; furthermore, high-frequency stimulation elicits synaptic facilitation, instead of normal synaptic depression, and the degree of facilitation is highly sensitive to the amount of cytoplasmic calcium buffering. In Cplx 2-null adrenal chromaffin cells, we also find decreased and desynchronized evoked release, and identify a significant reduction in the vesicle pool close to the calcium channels (immediately releasable pool, IRP). Viral transduction with either Cplx 1 or 2 rescues both the size of the evoked response and the synchronicity of release, and it restores the IRP size. Our findings in two model systems are mutually compatible and indicate a role of Cplx 1 and 2 in facilitating vesicle priming, and also lead to the new hypothesis that Cplxs may synchronize vesicle release by promoting coupling between secretory vesicles and calcium channels.
authors: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2520, USA.
authors: Ming-Yi
authors: MY
authors: Lin
authors: Joyce G
authors: JG
authors: Rohan
authors: Haijiang
authors: H
authors: Cai
authors: Kerstin
authors: K
authors: Reim
authors: Chien-Ping
authors: CP
authors: Ko
authors: Robert H
authors: RH
authors: Chow
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D019439:Chromaffin Cells / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology; D022142:Secretory Vesicles / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; C095992:complexin I; C095993:complexin II
references: Eur J Neurosci. 1998 Jun;10(6):2143-52
references: 9753100
references: Nat Neurosci. 2007 Oct;10(10):1235-7
references: 17873870
references: Curr Biol. 2011 Jan 25;21(2):97-105
references: 21215634
references: Nat Struct Mol Biol. 2010 Mar;17(3):325-31
references: 20173762
references: Neuron. 2009 May 28;62(4):539-54
references: 19477155
references: J Neurosci. 2009 Jun 24;29(25):7991-8004
references: 19553439
references: Science. 2006 Aug 4;313(5787):676-80
references: 16794037
references: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):E304-13
references: 21705659
references: Neuron. 2009 Aug 27;63(4):482-96
references: 19709630
references: Science. 2009 Jan 23;323(5913):516-21
references: 19164751
references: Nat Struct Mol Biol. 2006 Aug;13(8):748-50
references: 16845390
references: J Pharmacol Sci. 2003 Jun;92(2):79-83
references: 12832834
references: Biochemistry. 2009 Feb 3;48(4):657-9
references: 19128031
references: Neuron. 1999 Jul;23(3):607-15
references: 10433271
references: Nat Struct Mol Biol. 2010 Mar;17(3):318-24
references: 20173763
references: J Physiol. 1981 Feb;311:307-24
references: 6267255
references: J Neurophysiol. 2005 Nov;94(5):3278-91
references: 16033942
references: Cell. 2001 Jan 12;104(1):71-81
references: 11163241
references: Neuron. 2010 Dec 9;68(5):907-20
references: 21145004
references: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19538-43
references: 19033464
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11680-5
references: 11562488
references: Curr Biol. 2011 Jan 25;21(2):106-13
references: 21215631
references: Neuron. 2002 Dec 5;36(5):897-908
references: 12467593
references: Neuron. 2007 Jul 5;55(1):11-24
references: 17610814
references: Traffic. 2008 Sep;9(9):1403-13
references: 18445121
references: Brain Cell Biol. 2008 Dec;36(5-6):173-89
references: 19132534
references: J Biol Chem. 1998 Jul 17;273(29):18060-6
references: 9660762
references: J Neurosci. 2004 Jul 7;24(27):6127-32
references: 15240804
references: Diabetes. 2010 May;59(5):1192-201
references: 20150285
references: Nat Struct Mol Biol. 2006 Mar;13(3):209-17
references: 16491093
references: J Cell Sci. 2005 May 15;118(Pt 10):2239-46
references: 15870114
references: J Neurosci. 2012 Feb 22;32(8):2877-85
references: 22357870
references: Neuron. 2009 Nov 12;64(3):367-80
references: 19914185
references: Ann N Y Acad Sci. 2002 Oct;971:641-6
references: 12438199
references: Neuron. 1994 Nov;13(5):1119-29
references: 7946349
references: J Physiol. 1954 Jun 28;124(3):560-73
references: 13175199
references: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7875-80
references: 18505837
references: Mol Cell Neurosci. 2010 Dec;45(4):389-97
references: 20678575
references: Endocrinology. 2007 Apr;148(4):1605-14
references: 17204559
references: Cell. 2006 Sep 22;126(6):1175-87
references: 16990140
references: J Neurosci. 2012 Dec 12;32(50):18234-45
references: 23238737
references: Pflugers Arch. 1995 Jun;430(2):213-9
references: 7675631
references: Biochem J. 1999 Sep 15;342 Pt 3:497-501
references: 10477258
references: J Neurosci. 2006 Jan 11;26(2):632-43
references: 16407561
references: EMBO J. 2012 Aug 1;31(15):3270-81
references: 22705946