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Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems

Lin, Ming-Yi and Rohan, Joyce G. and Cai, Haijiang and Reim, Kerstin and Ko, Chien-Ping and Chow, Robert H. (2013) Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems. Journal of Physiology, 591 (10). pp. 2463-2473. ISSN 0022-3751. PMCID PMC3678037. doi:10.1113/jphysiol.2012.244517. https://resolver.caltech.edu/CaltechAUTHORS:20130621-083121898

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1113/jphysiol.2012.244517 DOIArticle
http://jp.physoc.org/content/591/10/2463PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678037/PubMed CentralArticle
Additional Information:© 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society. Received 6 September 2012; accepted after revision 4 February 2013; first published online 11 February 2013. We acknowledge the support of the following: NIH GM85791 (R.H.C.), NIH K18DK091445 (R.H.C.), NIH DK60623 (R.H.C.), Human Frontiers Science Program (to T.D. Parsons, N. Brose, G. Borst and R.H. Chow), NIH NS063296 (C.-P.K.), Deutsche Forschungsgemeinschaft (N.B. and K.R.), NIH F32GM088967 (J.G.R.). We would also like to thank the following for critical feedback: ErwinNeher, Rainhard Jahn,Nils Brose, Dion Dickman, Mark Rich, Kathrin Engisch, Kassandra Kisler, Jung Hwa Cho, Reymundo Dominguez, and Robert Farley. Author contributions: M.-Y.L. and J.G.R. contributed equally to the work. M.-Y.L. performed the immunostaining and electrophysiology in mouse NMJs. J.G.R. performed the electrophysiology in chromaffin cells. M.-Y.L. and J.G.R. collected and analysed the data. H.C. performed the initial preliminary experiments in chromaffin cells. K.R. provided critical input for the experiment and manuscript. R.H.C. and C.-P.K. co-supervised the experiment design and data interpretation. M.-Y.L., J.G.R., R.H.C. wrote the manuscript with inputs from K.R. and C.-P.K. All authors approved the final version of the manuscript.
Funders:
Funding AgencyGrant Number
NIHGM85791
NIHK18DK091445
NIHDK60623
Human Frontier Science ProgramUNSPECIFIED
NIHNS063296
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
NIH Postdoctoral FellowshipF32GM088967
Issue or Number:10
PubMed Central ID:PMC3678037
DOI:10.1113/jphysiol.2012.244517
Record Number:CaltechAUTHORS:20130621-083121898
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130621-083121898
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39015
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Jun 2013 16:14
Last Modified:09 Nov 2021 23:41

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