GTP Hydrolysis by the Rho Family GTPase TC10 Promotes Exocytic Vesicle Fusion

• Published in: Developmental cell Vol. 11; no. 3; pp. 411 - 421
• Main Authors: Kawase, Kazuho, Nakamura, Takeshi, Takaya, Akiyuki, Aoki, Kazuhiro, Namikawa, Kazuhiko, Kiyama, Hiroshi, Inagaki, Shuichiro, Takemoto, Hiroshi, Saltiel, Alan R., Matsuda, Michiyuki
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.09.2006; Cell Press
• Subjects: Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Membrane - enzymology; Cell Membrane - metabolism; Cell Movement; Cell physiology; CELLBIO; Cercopithecus aethiops; COS Cells; Enzyme Activation; Epidermal Growth Factor - pharmacology; Exocytosis; Fundamental and applied biological sciences. Psychology; Guanosine Triphosphate - metabolism; HeLa Cells; Humans; Hydrolysis; Models, Biological; Molecular and cellular biology; Pseudopodia - physiology; rho GTP-Binding Proteins - chemistry; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; RNA Interference; SIGNALING; Transfection; CELLBIO; SIGNALING; GTP; Enzyme; Triphosphoric monoester hydrolases; Development; dGTPase; Hydrolases; Esterases
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2006.07.008

TC10, a Rho family GTPase, has been shown to play an important role in the exocytosis of GLUT4 and other proteins, primarily by tethering the vesicles at the plasma membrane. Using a newly developed probe based on fluorescence resonance energy transfer, we found that TC10 activity at tethered vesicles dropped immediately before vesicle fusion in HeLa cells stimulated with epidermal growth factor (EGF), suggesting that GTP hydrolysis by TC10 is a critical step in vesicle fusion. In support of this model, a GTPase-deficient TC10 mutant potently inhibited EGF-induced vesicular fusion in HeLa cells and depolarization-induced neuronal secretion. Furthermore, we found that GTP hydrolysis by TC10 in the vicinity of the plasma membrane was dependent on Rac and the redox-regulated Rho GAP, p190RhoGAP-A. We propose that an EGF-stimulated GAP accelerates GTP hydrolysis of TC10, thereby promoting vesicle fusion.