Limits...
Roles of myosin Va and Rab3D in membrane remodeling of immature secretory granules.

Kögel T, Gerdes HH - Cell. Mol. Neurobiol. (2010)

Bottom Line: In PC12 cells, these immature SGs (ISGs) are transported within seconds to the cell cortex, where they move along actin filaments and complete maturation.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.

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.

Show MeSH

Related in: MedlinePlus

Model proposing the interaction of ISGs with F-actin. The scheme illustrates the putative anchorage of myosin Va to ISGs. Rab3D associates with the ISG membrane in the GTP-bound form and recruits the F-actin-dependent motor protein myosin Va through a not yet identified effector protein (white box with “?”)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3008937&req=5

Fig2: Model proposing the interaction of ISGs with F-actin. The scheme illustrates the putative anchorage of myosin Va to ISGs. Rab3D associates with the ISG membrane in the GTP-bound form and recruits the F-actin-dependent motor protein myosin Va through a not yet identified effector protein (white box with “?”)

Mentions: In analogy to melanosomes where myosin Va is bound via melanophilin and Rab27 (Hammer and Wu 2002; Fukuda 2008), it is conceivable that synaptotagmin-like effector proteins mediate the putative interaction of myosin Va and Rab3D (Fig. 2). Neuroendocrine cells express several such effectors including granuphilin, Noc2, MyRIP, rabphilin, and RIM2 (Fukuda et al. 2002, 2004; Fukuda 2003a, b, 2004, 2005a; Desnos et al. 2003; Waselle et al. 2003). While granuphilin, MyRIP, rabphilin, and RIM2 have been implicated in the final exocytosis step, several lines of evidence indicate Noc2 as a promising candidate to regulate an earlier step in SG trafficking, i.e., to link myosin Va to ISG-associated Rab3D (Fig. 2). One line of support was obtained from Noc2−/− mice, where exocrine cells contained SGs of abnormally large size and irregular shape (Shibasaki and Seino 2005). This observation is reminiscent of studies on Rab3D-knockout mice, in which an increase in granular size in some exocrine cell types was reported (Riedel et al. 2002). Furthermore, in Noc2−/− mice the regulated release of insulin secreting cells was shown to be impaired. Although these mice displayed normal glucose levels, the amount of insulin released under stress conditions was inappropriate and the mice became hyperglycemic (Matsumoto et al. 2004). These symptoms might be the result of impaired proinsulin processing, reminiscent of our data on the effect of compromised Rab3D on cargo processing in PC12 cells. Hence, it will be interesting to investigate whether Noc2 functions in SG maturation in concert with Rab3D and myosin Va.Fig. 2


Roles of myosin Va and Rab3D in membrane remodeling of immature secretory granules.

Kögel T, Gerdes HH - Cell. Mol. Neurobiol. (2010)

Model proposing the interaction of ISGs with F-actin. The scheme illustrates the putative anchorage of myosin Va to ISGs. Rab3D associates with the ISG membrane in the GTP-bound form and recruits the F-actin-dependent motor protein myosin Va through a not yet identified effector protein (white box with “?”)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008937&req=5

Fig2: Model proposing the interaction of ISGs with F-actin. The scheme illustrates the putative anchorage of myosin Va to ISGs. Rab3D associates with the ISG membrane in the GTP-bound form and recruits the F-actin-dependent motor protein myosin Va through a not yet identified effector protein (white box with “?”)
Mentions: In analogy to melanosomes where myosin Va is bound via melanophilin and Rab27 (Hammer and Wu 2002; Fukuda 2008), it is conceivable that synaptotagmin-like effector proteins mediate the putative interaction of myosin Va and Rab3D (Fig. 2). Neuroendocrine cells express several such effectors including granuphilin, Noc2, MyRIP, rabphilin, and RIM2 (Fukuda et al. 2002, 2004; Fukuda 2003a, b, 2004, 2005a; Desnos et al. 2003; Waselle et al. 2003). While granuphilin, MyRIP, rabphilin, and RIM2 have been implicated in the final exocytosis step, several lines of evidence indicate Noc2 as a promising candidate to regulate an earlier step in SG trafficking, i.e., to link myosin Va to ISG-associated Rab3D (Fig. 2). One line of support was obtained from Noc2−/− mice, where exocrine cells contained SGs of abnormally large size and irregular shape (Shibasaki and Seino 2005). This observation is reminiscent of studies on Rab3D-knockout mice, in which an increase in granular size in some exocrine cell types was reported (Riedel et al. 2002). Furthermore, in Noc2−/− mice the regulated release of insulin secreting cells was shown to be impaired. Although these mice displayed normal glucose levels, the amount of insulin released under stress conditions was inappropriate and the mice became hyperglycemic (Matsumoto et al. 2004). These symptoms might be the result of impaired proinsulin processing, reminiscent of our data on the effect of compromised Rab3D on cargo processing in PC12 cells. Hence, it will be interesting to investigate whether Noc2 functions in SG maturation in concert with Rab3D and myosin Va.Fig. 2

Bottom Line: In PC12 cells, these immature SGs (ISGs) are transported within seconds to the cell cortex, where they move along actin filaments and complete maturation.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.

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.

Show MeSH
Related in: MedlinePlus