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J. Biol. Chem., Vol. 278, Issue 6, 4258-4267, February 7, 2003
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From the We report here that unlike what was suggested for
many vertebrate neurons, synaptic transmission in Lymnaea
stagnalis occurs independent of a physical interaction between
presynaptic calcium channels and a functional complement of SNARE
proteins. Instead, synaptic transmission in Lymnaea
requires the expression of a C-terminal splice variant of the
Lymnaea homolog to mammalian N- and P/Q-type calcium
channels. We show that the alternately spliced region physically
interacts with the scaffolding proteins Mint1 and CASK, and that
synaptic transmission is abolished following RNA interference knockdown
of CASK or after the injection of peptide sequences designed to disrupt
the calcium channel-Mint1 interactions. Our data suggest that Mint1 and
CASK may serve to localize the non-L-type channels at the active zone
and that synaptic transmission in invertebrate neurons utilizes a
mechanism for optimizing calcium entry, which occurs independently of a
physical association between calcium channels and SNARE proteins.
Calcium Channel Structural Determinants of Synaptic Transmission
between Identified Invertebrate Neurons*
§¶,
,,**,,,, Department of Molecular and Cellular
Neurobiology, Vrije Universiteit, Amsterdam, 108HV Netherlands, the
§ Departments of Physiology and Biophysics, and Anatomy and
Cell Biology, University of Calgary, Calgary T2N 4N1, Canada, and the
Department of Biological Sciences,
University of Alberta, Edmonton T6G 1E9, Canada
*
This work was supported in part by operating grants from the
Canadian Institutes of Health Research (to N. I. S. and G. W. Z.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by from Alberta Heritage Foundation for Medical
Research Studentships.
**
Recipient of a Canadian Institutes of Health Research postdoctoral
fellowship award.
§§
Recipient of a Senior Scholarship from Alberta Heritage
Foundation for Medical Research and is a Canadian Institutes of Health Research Investigator. To whom correspondence should be addressed: Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr., N. W., Calgary T2N 4N1, Canada. Tel.: 403-220-8687; Fax: 403-210-8106; E-mail: Zamponi@ucalgary.ca.
¶¶
Recipient of a Scientist Award from the Alberta
Heritage Foundation for Medical Research and is a Canadian Institutes
of Health Research Investigator.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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