title: Roles of myosin Va and Rab3D in membrane remodeling of immature secretory granules.
abstract: Neuroendocrine secretory granules (SGs) are formed at the trans-Golgi network (TGN) as immature intermediates. In PC12 cells, these immature SGs (ISGs) are transported within seconds to the cell cortex, where they move along actin filaments and complete maturation. This maturation process comprises acidification-dependent processing of cargo proteins, condensation of the SG matrix, and removal of membrane and proteins not destined to mature SGs (MSGs) into ISG-derived vesicles (IDVs). We investigated the roles of myosin Va and Rab3 isoforms in the maturation of ISGs in neuroendocrine PC12 cells. The expression of dominant-negative mutants of myosin Va or Rab3D blocked the removal of the endoprotease furin from ISGs. Furthermore, expression of mutant Rab3D, but not of mutant myosin Va, impaired cargo processing of SGs. In conclusion, our data suggest an implication of myosin Va and Rab3D in the maturation of SGs where they participate in overlapping but not identical tasks.
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kögel
authors.forename: Hans-Hermann
authors.initials: HH
authors.lastname: Gerdes
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D008954:Models, Biological; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C513081:Myo5a protein, rat; D024701:Myosin Type V; C492133:Rab3d protein, rat; D018995:Myosin Heavy Chains; D020692:rab3 GTP-Binding Proteins