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The Journal of Neuroscience, April 15, 1998, 18(8):2914-2922
A Ca2+-Independent Receptor for  -Latrotoxin, CIRL,
Mediates Effects on Secretion via Multiple Mechanisms
Mary A.
Bittner1,
Valery G.
Krasnoperov3,
Edward L.
Stuenkel2,
Alexander G.
Petrenko3, and
Ronald W.
Holz1
Departments of 1 Pharmacology and
2 Physiology, The University of Michigan Medical School,
Ann Arbor, Michigan 48109, and 3 Department of
Pharmacology, New York University Medical Center, New York, New York
10016
 -Latrotoxin (-Ltx), a component of black widow spider venom,
stimulates secretion from nerve terminals and from PC12 cells. In this
study we examine the effects of expression of a newly cloned
Ca2+-independent receptor for -Ltx (CIRL) on
secretion from bovine chromaffin cells. We first characterized the
effect of -Ltx on secretion from untransfected cells. -Ltx, by
binding in a Ca2+-independent manner
to an endogenous receptor, causes subsequent Ca2+-dependent secretion from intact cells. The
stimulation of secretion is correlated with Ca2+
influx caused by the toxin. In permeabilized cells in which the Ca2+ concentration is regulated by buffer, -Ltx
also enhances Ca2+-dependent secretion, indicating a
direct role of the endogenous receptor in the secretory pathway.
Expression of CIRL increased the sensitivity of intact and
permeabilized cells to the effects of -Ltx, demonstrating that this
protein is functional in coupling to secretion. Importantly, in the
absence of -Ltx, the expression of CIRL specifically inhibited the
ATP-dependent component of secretion in permeabilized cells without
affecting the ATP-independent secretion. This suggests that this
receptor modulates the normal function of the regulated secretory
pathway and that -Ltx may act by reversing the inhibitory effects of
the receptor.
Key words:
-latrotoxin; secretion; exocytosis; catecholamine; chromaffin cell; secretion kinetics
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882914-09$05.00/0
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