BACKGROUND: The Rho small G protein family, which includes the Rho, Rac and Cdc42 subfamilies, is implicated in various cell functions such as cell shape change, cell motility and cytokinesis, through the reorganization of actin filaments. Rho GDI is an inhibitory regulator of the Rho small G protein family and inhibits the Rho family dependent cell functions. Reorganization of actin filaments is also known to regulate Ca2+-dependent exocytosis. RESULTS: We have examined here whether the Rho family members are also involved in Ca2+-dependent exocytosis. We have found, by the use of the human growth hormone (GH) co-expression assay system on PC12 cells, that overexpression of Rho GDI inhibits high K+-induced, Ca2+-dependent GH release. This inhibitory action of Rho GDI is restored by co-expression of a dominant active mutant of RhoA or Rac1, but not of a dominant active mutant of Cdc42. C3 transferase, known to ADP-ribosylate Rho and to inhibit its function, also inhibits this GH release. Overexpression of a dominant active mutant of RhoA or Rac1 alone shows only a small effect on GH release. Moreover, immunocytochemical studies show that the overexpression of Rho GDI prevents a partial disruption of the cortical actin network which accompanies exocytosis. CONCLUSIONS: These results suggest that RhoA, Rac1 and Rho GDI are involved in Ca2+-dependent exocytosis at least partly through the reorganization of actin filaments, and that the activation of RhoA or Rac1 alone is not sufficient for this reaction.

This article has been cited by other articles:

				H. Amano, W. Ikeda, S. Kawano, M. Kajita, Y. Tamaru, N. Inoue, Y. Minami, A. Yamada, and Y. Takai Interaction and localization of Necl-5 and PDGF receptor beta at the leading edges of moving NIH3T3 cells: Implications for directional cell movement. Genes Cells, March 1, 2008; 13(3): 269 - 284. [Abstract] [Full Text] [PDF]

				R. McMullan and S. J. Nurrish Rho deep in thought Genes & Dev., November 1, 2007; 21(21): 2677 - 2682. [Full Text] [PDF]

				Y. Minami, W. Ikeda, M. Kajita, T. Fujito, H. Amano, Y. Tamaru, K. Kuramitsu, Y. Sakamoto, M. Monden, and Y. Takai Necl-5/Poliovirus Receptor Interacts in cis with Integrin {alpha}Vbeta3 and Regulates Its Clustering and Focal Complex Formation J. Biol. Chem., June 22, 2007; 282(25): 18481 - 18496. [Abstract] [Full Text] [PDF]

				T. Yamada, T. Sakisaka, S. Hisata, T. Baba, and Y. Takai RA-RhoGAP, Rap-activated Rho GTPase-activating Protein Implicated in Neurite Outgrowth through Rho J. Biol. Chem., September 23, 2005; 280(38): 33026 - 33034. [Abstract] [Full Text] [PDF]

				B. Zhang, Y. Zhang, M.-C. Dagher, and E. Shacter Rho GDP Dissociation Inhibitor Protects Cancer Cells against Drug-Induced Apoptosis Cancer Res., July 15, 2005; 65(14): 6054 - 6062. [Abstract] [Full Text] [PDF]

				S. Kakunaga, W. Ikeda, S. Itoh, M. Deguchi-Tawarada, T. Ohtsuka, A. Mizoguchi, and Y. Takai Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes J. Cell Sci., March 15, 2005; 118(6): 1267 - 1277. [Abstract] [Full Text] [PDF]

				H. Ishida, X. Zhang, K. Erickson, and P. Ray Botulinum Toxin Type A Targets RhoB to Inhibit Lysophosphatidic Acid-Stimulated Actin Reorganization and Acetylcholine Release in Nerve Growth Factor-Treated PC12 Cells J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 881 - 889. [Abstract] [Full Text] [PDF]

				T. Sakisaka, T. Baba, S. Tanaka, G. Izumi, M. Yasumi, and Y. Takai Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites J. Cell Biol., July 5, 2004; 166(1): 17 - 25. [Abstract] [Full Text] [PDF]

				J. Li, R. Luo, A. Kowluru, and G. Li Novel regulation by Rac1 of glucose- and forskolin-induced insulin secretion in INS-1 {beta}-cells Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E818 - E827. [Abstract] [Full Text] [PDF]

				Y. Takai, T. Sasaki, and T. Matozaki Small GTP-Binding Proteins Physiol Rev, January 1, 2001; 81(1): 153 - 208. [Abstract] [Full Text] [PDF]

				A. Jahraus, M. Egeberg, B. Hinner, A. Habermann, E. Sackman, A. Pralle, H. Faulstich, V. Rybin, H. Defacque, and G. Griffiths ATP-dependent Membrane Assembly of F-Actin Facilitates Membrane Fusion Mol. Biol. Cell, January 1, 2001; 12(1): 155 - 170. [Abstract] [Full Text]

				T. Sumi, K. Matsumoto, Y. Takai, and T. Nakamura Cofilin Phosphorylation and Actin Cytoskeletal Dynamics Regulated by Rho- and Cdc42-activated LIM-kinase 2 J. Cell Biol., December 27, 1999; 147(7): 1519 - 1532. [Abstract] [Full Text] [PDF]

				M. Umikawa, H. Obaishi, H. Nakanishi, K. Satoh-Horikawa, K. Takahashi, I. Hotta, Y. Matsuura, and Y. Takai Association of Frabin with the Actin Cytoskeleton Is Essential for Microspike Formation through Activation of Cdc42 Small G Protein J. Biol. Chem., September 3, 1999; 274(36): 25197 - 25200. [Abstract] [Full Text] [PDF]

				K. Nakano, K. Takaishi, A. Kodama, A. Mammoto, H. Shiozaki, M. Monden, and Y. Takai Distinct Actions and Cooperative Roles of ROCK and mDia in Rho Small G Protein-induced Reorganization of the Actin Cytoskeleton in Madin-Darby Canine Kidney Cells Mol. Biol. Cell, August 1, 1999; 10(8): 2481 - 2491. [Abstract] [Full Text]

				H. Imamura, K. Takaishi, K. Nakano, A. Kodama, H. Oishi, H. Shiozaki, M. Monden, T. Sasaki, and Y. Takai Rho and Rab Small G Proteins Coordinately Reorganize Stress Fibers and Focal Adhesions in MDCK Cells Mol. Biol. Cell, September 1, 1998; 9(9): 2561 - 2575. [Abstract] [Full Text]

				H. Obaishi, H. Nakanishi, K. Mandai, K. Satoh, A. Satoh, K. Takahashi, M. Miyahara, H. Nishioka, K. Takaishi, and Y. Takai Frabin, a Novel FGD1-related Actin Filament-binding Protein Capable of Changing Cell Shape and Activating c-Jun N-terminal Kinase J. Biol. Chem., July 24, 1998; 273(30): 18697 - 18700. [Abstract] [Full Text] [PDF]

				S. Gasman, S. Chasserot-Golaz, P. Hubert, D. Aunis, and M.-F. Bader Identification of a Potential Effector Pathway for the Trimeric Go Protein Associated with Secretory Granules. Go STIMULATES A GRANULE-BOUND PHOSPHATIDYLINOSITOL 4-KINASE BY ACTIVATING RhoA IN CHROMAFFIN CELLS J. Biol. Chem., July 3, 1998; 273(27): 16913 - 16920. [Abstract] [Full Text] [PDF]

				K. Takaishi, T. Sasaki, H. Kotani, H. Nishioka, and Y. Takai Regulation of Cell-Cell Adhesion by Rac and Rho Small G Proteins in MDCK Cells J. Cell Biol., November 17, 1997; 139(4): 1047 - 1059. [Abstract] [Full Text] [PDF]

				S. Orita, A. Naito, G. Sakaguchi, M. Maeda, H. Igarashi, T. Sasaki, and Y. Takai Physical and Functional Interactions of Doc2 and Munc13 in Ca2+-dependent Exocytotic Machinery J. Biol. Chem., June 27, 1997; 272(26): 16081 - 16084. [Abstract] [Full Text] [PDF]

				A. Harada, B. Furuta, K.-i. Takeuchi, M. Itakura, M. Takahashi, and M. Umeda Nadrin, a Novel Neuron-specific GTPase-activating Protein Involved in Regulated Exocytosis J. Biol. Chem., November 17, 2000; 275(47): 36885 - 36891. [Abstract] [Full Text] [PDF]