title: Rab27A and its effector MyRIP link secretory granules to F-actin and control their motion towards release sites.
abstract: The GTPase Rab27A interacts with myosin-VIIa and myosin-Va via MyRIP or melanophilin and mediates melanosome binding to actin. Here we show that Rab27A and MyRIP are associated with secretory granules (SGs) in adrenal chromaffin cells and PC12 cells. Overexpression of Rab27A, GTPase-deficient Rab27A-Q78L, or MyRIP reduced secretory responses of PC12 cells. Amperometric recordings of single adrenal chromaffin cells revealed that Rab27A-Q78L and MyRIP reduced the sustained component of release. Moreover, these effects on secretion were partly suppressed by the actin-depolymerizing drug latrunculin but strengthened by jasplakinolide, which stabilizes the actin cortex. Finally, MyRIP and Rab27A-Q78L restricted the motion of SGs in the subplasmalemmal region of PC12 cells, as measured by evanescent-wave fluorescence microscopy. In contrast, the Rab27A-binding domain of MyRIP and a MyRIP construct that interacts with myosin-Va but not with actin increased the mobility of SGs. We propose that Rab27A and MyRIP link SGs to F-actin and control their motion toward release sites through the actin cortex.
authors: Centre National de la Recherche Scientifique (CNRS) UPR 1929, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors: Claire
authors: C
authors: Desnos
authors: Jean-Sébastien
authors: JS
authors: Schonn
authors: Sébastien
authors: S
authors: Huet
authors: Viet Samuel
authors: VS
authors: Tran
authors: Aziz
authors: A
authors: El-Amraoui
authors: Graça
authors: G
authors: Raposo
authors: Isabelle
authors: I
authors: Fanget
authors: Catherine
authors: C
authors: Chapuis
authors: Gaël
authors: G
authors: Ménasché
authors: Geneviève
authors: G
authors: de Saint Basile
authors: Christine
authors: C
authors: Petit
authors: Sophie
authors: S
authors: Cribier
authors: Jean-Pierre
authors: JP
authors: Henry
authors: François
authors: F
authors: Darchen
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D047630:Depsipeptides; D005089:Exocytosis / Q000187:drug effects / Q000235:genetics; D008854:Microscopy, Electron; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D016716:PC12 Cells; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D047630:Depsipeptides; C492410:MLPH protein, human; C492409:Mlph protein, rat; C513081:Myo5a protein, rat; D010456:Peptides, Cyclic; D013844:Thiazoles; D053778:Thiazolidines; D000075745:rab27 GTP-Binding Proteins; C057531:jasplakinolide; D024701:Myosin Type V; C512961:Rab27a protein, rat; D018995:Myosin Heavy Chains; D020691:rab GTP-Binding Proteins; C037067:latrunculin A