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The Journal of Neuroscience, May 21, 2008, 28(21):5594-5601; doi:10.1523/JNEUROSCI.5672-07.2008

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Cellular/Molecular
CAPS Facilitates Filling of the Rapidly Releasable Pool of Large Dense-Core Vesicles

Yuanyuan Liu,¹ Claudia Schirra,¹ David R. Stevens,¹ Ulf Matti,¹ Dina Speidel,² Detlef Hof,¹ Dieter Bruns,¹ Nils Brose,² and Jens Rettig¹

¹Institut für Physiologie, Universität des Saarlandes, D-66421 Homburg/Saar, Germany, and ²Max-Planck-Institut für Experimentelle Medizin, Abteilung Molekulare Neurobiologie, D-37075 Göttingen, Germany

Correspondence should be addressed to Dr. Jens Rettig, Institut für Physiologie, Universität des Saarlandes, Gebäude 59, Kirrberger Strasse 8, 66421 Homburg/Saar, Germany. Email: jrettig{at}uks.eu

Calcium-activator protein for secretion (CAPS) is a cytosolic protein that associates with large dense-core vesicles and is involved in their secretion. Mammals express two CAPS isoforms, which share a similar domain structure including a Munc13 homology domain that is believed to be involved in the priming of secretory vesicles. A variety of studies designed to perturb CAPS function indicate that CAPS is involved in the secretion of large dense-core vesicles, but where in the secretory pathway CAPS acts is still under debate. Mice in which one allele of the CAPS-1 gene is deleted exhibit a deficit in catecholamine secretion from chromaffin cells. We have examined catecholamine secretion from chromaffin cells in which both CAPS genes were deleted and show that the deletion of both CAPS isoforms causes a strong reduction in the pool of rapidly releasable chromaffin granules and of sustained release during ongoing stimulation. We conclude that CAPS is required for the adequate refilling and/or maintenance of a rapidly releasable granule pool.

Key words: exocytosis; priming; docking; rapidly releasable pool; slowly releasable pool; chromaffin cell

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Received Dec. 21, 2007; revised March 20, 2008; accepted April 17, 2008.

Correspondence should be addressed to Dr. Jens Rettig, Institut für Physiologie, Universität des Saarlandes, Gebäude 59, Kirrberger Strasse 8, 66421 Homburg/Saar, Germany. Email: jrettig{at}uks.eu

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