Myosin Va Mediates Docking of Secretory Granules at the Plasma Membrane

Desnos, Claire; Huet, Sébastien; Fanget, Isabelle; Chapuis, Catherine; Böttiger, Caroline; Racine, Victor; Sibarita, Jean‐Baptiste; Henry, Jean‐Pierre; Darchen, François

doi:10.1523/jneurosci.1228-07.2007

Cited by 84 publications

(101 citation statements)

References 57 publications

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“…Although outside the scope of the present study, it would be worth testing whether Myosin-5a could be the actual molecular motor involved in the IC87114-mediated translocation of secretory granules to the plasma membrane 40 . Our estimation of the speed of the translocating vesicles (11.5 ± 1.1 nm s − 1 ) is slower than that previously reported for vesicles under depolarization (34 ± 17 nm s effectors such as scinderin 47 , which normally contribute to the translocation of secretory vesicles via their loosening effect on the cortical actin network.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

et al. 2011

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neurosecretory vesicles undergo docking and priming before Ca 2 + -dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P 2 ) is required for exocytosis, its precise contribution is still unclear. Here we show that inhibition of the p110δ isoform of PI3-kinase by IC87114 promotes a transient increase in PtdIns(4,5)P 2 , leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5)P 2 increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. our results demonstrate that a rise in PtdIns(4,5)P 2 is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5)P 2, therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

et al. 2011

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“…From stacks of images, 2-dimensional (x, y) trajectories were obtained by single particle tracking using MIA software. Mean square displacement (MSD) in the x,y plane was calculated as described 25,49 and selected using locally written routines (MatLab, The MathWorks, USA). Frame-to-frame rates of movement were calculated and averaged over each period of directed motion.…”

Section: Evanescent Wave Fluorescence Microscopy (Tirfm)mentioning

confidence: 99%

Rab27a and Rab27b control different steps of the exosome secretion pathway

Carmo²,

et al. 2009

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Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using a RNA interference screen, we identified five RabGTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to act in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms play different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (SYTL4) and Slac2b (EXPH5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and open ways to manipulate exosome secretion in vivo.3

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“…pcDNA3-mycRab11b was a gift from M. Cormont (INSERM U895, Centre Méditerranéen de Médecine Moléculaire, Nice, France). Vectors encoding human Myc-tagged-Myrip constructs, human myosin Va, and NPY constructs have been described previously (El-Amraoui et al, 2002;Desnos et al, 2007b). To generate a Myrip rescue construct, three silent mutations corresponding to nucleotides 2, 9 and 11 of Myrip-siRNA1 (sense strand) were introduced by PCR-based mutagenesis in the Myctagged Myrip construct.…”

Section: Constructsmentioning

confidence: 99%

“…MyoVa is associated with SGs and its inhibition impairs SG docking and secretion (Rose et al, 2003;Rudolf et al, 2003Rudolf et al, , 2011Varadi et al, 2005;Desnos et al, 2007b). MyoVa is recruited on SGs by the GTPase Rab27a and Myrip (Fukuda and Kuroda, 2002;Desnos et al, 2003;Waselle et al, 2003;Imai et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Myrip Couples the Capture of Secretory Granules by the Actin-Rich Cell Cortex and Their Attachment to the Plasma Membrane

Huet¹,

Fanget²,

Jouannot³

et al. 2012

J. Neurosci.

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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.

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Myosin Va Mediates Docking of Secretory Granules at the Plasma Membrane

Cited by 84 publications

References 57 publications

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

Rab27a and Rab27b control different steps of the exosome secretion pathway

Myrip Couples the Capture of Secretory Granules by the Actin-Rich Cell Cortex and Their Attachment to the Plasma Membrane

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