title: Rab3D is critical for secretory granule maturation in PC12 cells.
abstract: Neuropeptide- and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kögel
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Rudolf
authors.forename: Erlend
authors.initials: E
authors.lastname: Hodneland
authors.forename: John
authors.initials: J
authors.lastname: Copier
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Tooze
authors.forename: Hans-Hermann
authors.initials: HH
authors.lastname: Gerdes
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045683:Furin / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D053381:Secretogranin II / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D050505:Mutant Proteins; D053381:Secretogranin II; C506141:secretogranin 2, rat; D045683:Furin; C492133:Rab3d protein, rat; D020692:rab3 GTP-Binding Proteins