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Myrip couples the capture of secretory granules by the actin-rich cell cortex and their attachment to the plasma membrane.
Huet S., Fanget I., Jouannot O., Meireles P., Zeiske T., Larochette N., Darchen F., Desnos C.
Journal of Neuroscience 32, 7 (2012) 2564-77 - http://www.hal.inserm.fr/inserm-00679404
(22396429)
Myrip couples the capture of secretory granules by the actin-rich cell cortex and their attachment to the plasma membrane.
Sébastien Huet1, 2, Isabelle Fanget3, Ouardane Jouannot3, Patricia Meireles3, Tim Zeiske3, Nathanaël Larochette3, François Darchen () 3, Claire Desnos3
1 :  IGDR - Institut de Génétique et Développement de Rennes
http://igdr.univ-rennes1.fr/
Université de Rennes 1 – CNRS : UMR6290 – Biosit
Faculté de Médecine - CS 34317 2 Av du Professeur Léon Bernard 35043 Rennes Cedex
France
2 :  UEB - Université européenne de Bretagne
http://www.ueb.eu/
PRES Université Européenne de Bretagne [UEB]
5 Boulevard Laënnec 35000 Rennes
France
3 :  Laboratoire de dynamique membranaire et maladies neurologiques
CNRS : UMR8192 – Université Paris V - Paris Descartes
13, rue Pierre et Marie Curie, F-75005 Paris
France
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.
Sciences du Vivant/Biologie cellulaire
Anglais
0270-6474

Articles dans des revues avec comité de lecture
10.1523/JNEUROSCI.2724-11.2012
Journal of Neuroscience (J Neurosci)
Publisher Society for Neuroscience
ISSN 0270-6474 (eISSN : 1529-2401)
internationale
15/02/2012
32
7
2564-77

Actins – Cell Adhesion – Cell Line – Tumor – Cell Membrane – Enterochromaffin Cells – Exocytosis – Humans – Protein Binding – Secretory Vesicles – Vesicular Transport Proteins
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