title: Myrip couples the capture of secretory granules by the actin-rich cell cortex and their attachment to the plasma membrane.
abstract: Exocytosis of secretory granules (SGs) requires their delivery to the actin-rich cell cortex followed by their attachment to the plasma membrane (PM). How these reactions are executed and coordinated is still unclear. Myrip, which is also known as Slac-2c, binds to the SG-associated GTPase Rab27 and is thought to promote the delivery of SGs to the PM by recruiting the molecular motor myosin Va. Myrip also interacts with actin and the exocyst complex, suggesting that it may exert multiple roles in the secretory process. By combining total internal reflection fluorescence microscopy, single-particle tracking, a photoconversion-based assay, and mathematical modeling, we show that, in human enterochromaffin cells, Myrip (1) inhibits a class of SG motion characterized by fast and directed movement, suggesting that it facilitates the dissociation of SGs from microtubules; (2) enhances their motion toward the PM and the probability of SG attachment to the PM; and (3) increases the characteristic time of immobilization at the PM, indicating that it is a component of the molecular machinery that tether SGs to the PM. Remarkably, while the first two effects of Myrip depend on its ability to recruit myosin Va on SGs, the third is myosin Va independent but relies on the C-terminal domain of Myrip. We conclude that Myrip couples the retention of SGs in the cell cortex, their transport to the PM, and their attachment to the PM, and thus promotes secretion. These three steps of the secretory process are thus intimately coordinated.
authors.affiliation: Centre National de la Recherche Scientifique, UMR 6290, Institut Génétique et Développement de Rennes and Faculté de Médecine, Université Rennes 1, Université Européenne de Bretagne, Fédération de recherche Biosit, F-35043 Rennes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Huet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fanget
authors.forename: Ouardane
authors.initials: O
authors.lastname: Jouannot
authors.forename: Patricia
authors.initials: P
authors.lastname: Meireles
authors.forename: Tim
authors.initials: T
authors.lastname: Zeiske
authors.forename: Nathanaël
authors.initials: N
authors.lastname: Larochette
authors.forename: François
authors.initials: F
authors.lastname: Darchen
authors.forename: Claire
authors.initials: C
authors.lastname: Desnos
mesh_terms: D000199:Actins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000648:ultrastructure; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; C501262:MYRIP protein, human; D033921:Vesicular Transport Proteins