Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenal Glands / cytology
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Animals
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Biological Transport / genetics
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Biological Transport / physiology
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium-Binding Proteins / deficiency
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Calcium-Binding Proteins / physiology*
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Catecholamines / metabolism
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Cells, Cultured
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Chromaffin Cells / ultrastructure*
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / metabolism
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Embryo, Mammalian
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Green Fluorescent Proteins / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Mice
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Mice, Knockout
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Microscopy, Electron, Transmission / methods
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / physiology*
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Patch-Clamp Techniques
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Photolysis
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Secretory Vesicles / drug effects
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Secretory Vesicles / physiology*
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Secretory Vesicles / ultrastructure
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Transfection / methods
Substances
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CAPS2 protein, mouse
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Cadps protein, mouse
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Calcium-Binding Proteins
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Catecholamines
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Nerve Tissue Proteins
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Green Fluorescent Proteins
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2-nitrophenyl-EGTA
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Egtazic Acid
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Calcium