title: Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics.
abstract: In mammalian cells, the Golgi apparatus is a ribbon-like, compact structure composed of multiple membrane stacks connected by tubular bridges. Microtubules are known to be important to Golgi integrity, but the role of the actin cytoskeleton in the maintenance of Golgi architecture remains unclear. Here we show that an increase in Rho activity, either by treatment of cells with lysophosphatidic acid or by expression of constitutively active mutants, resulted in pronounced fragmentation of the Golgi complex into ministacks. Golgi dispersion required the involvement of mDia1 formin, a downstream target of Rho and a potent activator of actin polymerization; moreover, constitutively active mDia1, in and of itself, was sufficient for Golgi dispersion. The dispersion process was accompanied by formation of dynamic F-actin patches in the Golgi area. Experiments with cytoskeletal inhibitors (e.g., latrunculin B, blebbistatin, and Taxol) revealed that actin polymerization, myosin-II-driven contractility, and microtubule-based intracellular movement were all involved in the process of Golgi dispersion induced by Rho-mDia1 activation. Live imaging of Golgi recovery revealed that fusion of the small Golgi stacks into larger compartments was repressed in cells with active mDia1. Furthermore, the formation of Rab6-positive transport vesicles derived from the Golgi complex was enhanced upon activation of the Rho-mDia1 pathway. Transient localization of mDia1 to Rab6-positive vesicles was detected in cells expressing active RhoA. Thus, the Rho-mDia1 pathway is involved in regulation of the Golgi structure, affecting remodeling of Golgi membranes.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Zilberman
authors.forename: Naila O
authors.initials: NO
authors.lastname: Alieva
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miserey-Lenkei
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lichtenstein
authors.forename: Zvi
authors.initials: Z
authors.lastname: Kam
authors.forename: Helena
authors.initials: H
authors.lastname: Sabanay
authors.forename: Alexander
authors.initials: A
authors.lastname: Bershadsky
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D024462:Myosin Type II / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D050257:Tubulin Modulators / Q000494:pharmacology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; C094135:Rab6 protein; D050257:Tubulin Modulators; C066737:RHOA protein, human; D024462:Myosin Type II; D020691:rab GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D017239:Paclitaxel