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

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.

[1]  Shigeki Watanabe,et al.  CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons , 2008, The Journal of cell biology.

[2]  Qian Ge,et al.  PKA Activation Bypasses the Requirement for UNC-31 in the Docking of Dense Core Vesicles from C. elegans Neurons , 2007, Neuron.

[3]  Nils Brose,et al.  CAPS-1 and CAPS-2 Are Essential Synaptic Vesicle Priming Proteins , 2007, Cell.

[4]  J. Richmond,et al.  Tomosyn Negatively Regulates CAPS-Dependent Peptide Release at Caenorhabditis elegans Synapses , 2007, The Journal of Neuroscience.

[5]  S. Sugita,et al.  Ca2+-dependent Activator Protein for Secretion 1 Is Critical for Constitutive and Regulated Exocytosis but Not for Loading of Transmitters into Dense Core Vesicles* , 2007, Journal of Biological Chemistry.

[6]  E. Jorgensen,et al.  UNC-31 (CAPS) Is Required for Dense-Core Vesicle But Not Synaptic Vesicle Exocytosis in Caenorhabditis elegans , 2007, The Journal of Neuroscience.

[7]  L. Kang,et al.  Munc13-1 is required for the sustained release of insulin from pancreatic beta cells. , 2006, Cell metabolism.

[8]  J. Kaplan,et al.  UNC-13 Interaction with Syntaxin Is Required for Synaptic Transmission , 2005, Current Biology.

[9]  U. Matti,et al.  Identification of the Minimal Protein Domain Required for Priming Activity of Munc13-1 , 2005, Current Biology.

[10]  N. Grishin,et al.  A minimal domain responsible for Munc13 activity , 2005, Nature Structural &Molecular Biology.

[11]  Xi C. He,et al.  Reply to Re-examination of P-PTEN staining patterns in the intestinal crypt , 2005, Nature Genetics.

[12]  Thomas Voets,et al.  CAPS1 Regulates Catecholamine Loading of Large Dense-Core Vesicles , 2005, Neuron.

[13]  V. A. Klenchin,et al.  CAPS Acts at a Prefusion Step in Dense-Core Vesicle Exocytosis as a PIP2 Binding Protein , 2004, Neuron.

[14]  J. B. Sørensen.  Formation, stabilisation and fusion of the readily releasable pool of secretory vesicles , 2004, Pflügers Archiv.

[15]  Nils Brose,et al.  A Family of Ca2+-Dependent Activator Proteins for Secretion , 2003, Journal of Biological Chemistry.

[16]  Alan Morgan,et al.  Secretory granule exocytosis. , 2003, Physiological reviews.

[17]  Stephen W Scherer,et al.  Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family. , 2003, Genomics.

[18]  E. Neher,et al.  Emerging Roles of Presynaptic Proteins in Ca++-Triggered Exocytosis , 2002, Science.

[19]  V. A. Klenchin,et al.  Membrane Association Domains in Ca2+-dependent Activator Protein for Secretion Mediate Plasma Membrane and Dense-core Vesicle Binding Required for Ca2+-dependent Exocytosis* , 2002, The Journal of Biological Chemistry.

[20]  E. Neher,et al.  The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[21]  K. Broadie,et al.  Drosophila CAPS Is an Essential Gene that Regulates Dense-Core Vesicle Release and Synaptic Vesicle Fusion , 2001, Neuron.

[22]  T. Voets.  Dissection of Three Ca2+-Dependent Steps Leading to Secretion in Chromaffin Cells from Mouse Adrenal Slices , 2000, Neuron.

[23]  E. Neher,et al.  Munc13‐1 acts as a priming factor for large dense‐core vesicles in bovine chromaffin cells , 2000, The EMBO journal.

[24]  K. Hofmann,et al.  Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform. , 2000, The Biochemical journal.

[25]  M. Kreft,et al.  Rapid regulated dense-core vesicle exocytosis requires the CAPS protein. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Kendal Broadie,et al.  Drosophila Unc-13 is essential for synaptic transmission , 1999, Nature Neuroscience.

[27]  E. Jorgensen,et al.  UNC-13 is required for synaptic vesicle fusion in C. elegans , 1999, Nature Neuroscience.

[28]  T. Martin,et al.  Ca2+-Dependent Activator Protein for Secretion Is Critical for the Fusion of Dense-Core Vesicles with the Membrane in Calf Adrenal Chromaffin Cells , 1999, The Journal of Neuroscience.

[29]  U. Ashery,et al.  An efficient method for infection of adrenal chromaffin cells using the Semliki Forest virus gene expression system. , 1999, European journal of cell biology.

[30]  N. Brose,et al.  Differential expression of two novel Munc13 proteins in rat brain. , 1999, The Biochemical journal.

[31]  T. Martin,et al.  Ca(2+)-dependent activator protein for secretion is critical for the fusion of dense-core vesicles with the membrane in calf adrenal chromaffin cells. , 1999, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  W. Balch,et al.  Differential Regulation of Exocytosis by Calcium and CAPS in Semi-Intact Synaptosomes , 1998, Neuron.

[33]  E. Floor,et al.  CAPS (Mammalian UNC-31) Protein Localizes to Membranes Involved in Dense-Core Vesicle Exocytosis , 1998, Neuron.

[34]  K. Loyet,et al.  Novel Ca2+-binding Protein (CAPS) Related to UNC-31 Required for Ca2+-activated Exocytosis* , 1997, The Journal of Biological Chemistry.

[35]  E. Neher,et al.  Rapid Exocytosis in Single Chromaffin Cells Recorded from Mouse Adrenal Slices , 1997, The Journal of Neuroscience.

[36]  Cori Bargmann,et al.  The Caenorhabditis elegans unc-31 gene affects multiple nervous system-controlled functions. , 1993, Genetics.

[37]  J. Hay,et al.  Resolution of regulated secretion into sequential MgATP-dependent and calcium-dependent stages mediated by distinct cytosolic proteins , 1992, The Journal of cell biology.

[38]  T. Martin,et al.  A novel 145 kd brain cytosolic protein reconstitutes Ca2+-regulated secretion in permeable neuroendocrine cells , 1992, Cell.