Publication: Complexin II plays a positive role in Ca<sup>2+</sup>-triggered exocytosis by facilitating vesicle priming
Issued Date
2008-12-09
Resource Type
ISSN
10916490
00278424
00278424
Other identifier(s)
2-s2.0-58049220229
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Mahidol University
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SCOPUS
Bibliographic Citation
Proceedings of the National Academy of Sciences of the United States of America. Vol.105, No.49 (2008), 19538-19543
Suggested Citation
Haijiang Cai, Kerstin Reim, Frederique Varoqueaux, Sompol Tapechum, Kerstin Hill, Jakob B. Sørensen, Nils Brose, Robert H. Chow Complexin II plays a positive role in Ca<sup>2+</sup>-triggered exocytosis by facilitating vesicle priming. Proceedings of the National Academy of Sciences of the United States of America. Vol.105, No.49 (2008), 19538-19543. doi:10.1073/pnas.0810232105 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/19920
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Title
Complexin II plays a positive role in Ca<sup>2+</sup>-triggered exocytosis by facilitating vesicle priming
Abstract
SNARE-mediated exocytosis is a multistage process central to synaptic transmission and hormone release. Complexins (CPXs) are small proteins that bind very rapidly and with a high affinity to the SNARE core complex, where they have been proposed recently to inhibit exocytosis by clamping the complex and inhibiting membrane fusion. However, several other studies also suggest that CPXs are positive regulators of neurotransmitter release. Thus, whether CPXs are positive or negative regulators of exocytosis is not known, much less the stage in the vesicle life cycle at which they function. Here, we systematically dissect the vesicle stages leading up to exocytosis using a knockout-rescue strategy in a mammalian model system. We show that adrenal chromaffin cells from CPX II knockout mice exhibit markedly diminished releasable vesicle pools (comprising the readily and slowly releasable pools), while showing no change in the kinetics of fusion pore dilation or morphological vesicle docking. Overexpression of WT CPX II - but not of SNARE-binding-deficient mutants - restores the size of the the releasable pools in knockout cells, and in WT cells it markedly enlarges them. Our results show that CPXs regulate the size of the primed vesicle pools and have a positive role in Ca2+-triggered exocytosis. © 2008 by The National Academy of Sciences of the USA.