title: Secretory vesicle priming by CAPS is independent of its SNARE-binding MUN domain.
abstract: Priming of secretory vesicles is a prerequisite for their Ca(2+)-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. Munc13s execute their priming function through their MUN domain. Given that the MUN domain of Ca(2+)-dependent activator protein for secretion (CAPS) also binds syntaxin, it was assumed that CAPSs prime vesicles through the same mechanism as Munc13s. We studied naturally occurring splice variants of CAPS2 in CAPS1/CAPS2-deficient cells and found that CAPS2 primes vesicles independently of its MUN domain. Instead, the pleckstrin homology domain of CAPS2 seemingly is essential for its priming function. Our findings indicate a priming mode for secretory vesicles. This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action.
authors.affiliation: Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, Germany.
authors.forename: Cuc Quynh
authors.initials: CQ
authors.lastname: Nguyen Truong
authors.affiliation: Neurophysiology Group, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany; Department of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Nestvogel
authors.affiliation: Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Ratai
authors.affiliation: Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schirra
authors.affiliation: Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, Germany.
authors.forename: David R
authors.initials: DR
authors.lastname: Stevens
authors.affiliation: Department of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Neurophysiology Group, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany; Department of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: JeongSeop
authors.initials: J
authors.lastname: Rhee
authors.affiliation: Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, Germany. Electronic address: jrettig@uks.eu.
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism*; D019439:Chromaffin Cells / Q000378:metabolism; D005089:Exocytosis; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050600:SNARE Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: C480975:CAPS2 protein, mouse; C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins