ChemBridge Corporation Screening Compounds Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on February 28, 2008, 10.1073/pnas.0712373105
PNAS | March 11, 2008 | vol. 105 | no. 10 | 3998-4003


This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (2)
Google Scholar
Right arrow Articles by Schonn, J.-S.
Right arrow Articles by Sørensen, J. B.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schonn, J.-S.
Right arrow Articles by Sørensen, J. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

BIOLOGICAL SCIENCES / NEUROSCIENCE
Synaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells

Jean-Sébastien Schonn*,{dagger}, Anton Maximov{ddagger},§,¶,||, Ye Lao{ddagger},§,¶, Thomas C. Südhof{ddagger},§,¶,**, and Jakob B. Sørensen*,**

*Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany; and {ddagger}Departments of Neuroscience and §Molecular Genetics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390

Contributed by Thomas C. Südhof, December 31, 2007 (received for review November 29, 2007)

Synaptotagmin-1, the canonical isoform of the synaptotagmin family, is a Ca2+ sensor for fast synchronous neurotransmitter release in forebrain neurons and chromaffin cells. Even though deletion of synaptotagmin-1 abolishes fast exocytosis in chromaffin cells, it reduces overall secretion by only 20% because of the persistence of slow exocytosis. Therefore, another Ca2+ sensor dominates release in these cells. Synaptotagmin-7 has a higher Ca2+ affinity and slower binding kinetics than synaptotagmin-1, matching the proposed properties for the second, slower Ca2+ sensor. Here, we examined Ca2+-triggered exocytosis in chromaffin cells from KO mice lacking synaptotagmin-7, and from knockin mice containing normal levels of a mutant synaptotagmin-7 whose C2B domain does not bind Ca2+. In both types of mutant chromaffin cells, Ca2+-triggered exocytosis was decreased dramatically. Moreover, in chromaffin cells lacking both synaptotagmin-1 and -7, only a very slow release component, accounting for {approx}30% of WT exocytosis, persisted. These data establish synaptotagmin-7 as a major Ca2+ sensor for exocytosis in chromaffin cells, which, together with synaptotagmin-1, mediates almost all of the Ca2+ triggering of exocytosis in these cells, a surprising result, considering the lack of a role of synaptotagmin-7 in synaptic vesicle exocytosis.

amperometry | calcium-binding protein | capacitance | dense core vesicle | fusion

Author contributions: J.-S.S., A.M., T.C.S., and J.B.S. designed research; J.-S.S., A.M., and Y.L. performed research; J.-S.S., A.M., T.C.S., and J.B.S. analyzed data; and T.C.S. and J.B.S. wrote the paper.

{dagger}Present address: Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique UPR 1929, F-75005 Paris, France.

||Present address: Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0712373105/DC1.

**To whom correspondence may be addressed. E-mail: thomas.sudhof{at}utsouthwestern.edu or jsoeren{at}gwdg.de

© 2008 by The National Academy of Sciences of the USA


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Gustavsson, Y. Lao, A. Maximov, J.-C. Chuang, E. Kostromina, J. J. Repa, C. Li, G. K. Radda, T. C. Sudhof, and W. Han
Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice
PNAS, March 11, 2008; 105(10): 3992 - 3997.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Maximov, Y. Lao, H. Li, X. Chen, J. Rizo, J. B. Sorensen, and T. C. Sudhof
Genetic analysis of synaptotagmin-7 function in synaptic vesicle exocytosis
PNAS, March 11, 2008; 105(10): 3986 - 3991.
[Abstract] [Full Text] [PDF]