| ARHGAP18, a GTPase activating protein for RhoA, controls cell shape, spreading and motility. | |
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MedLine Citation:
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PMID: 21865595 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rho GTPases are molecular switches that transmit biochemical signals in response to extracellular stimuli to elicit changes in the actin cytoskeleton. Rho GTPases cycle between an active GTP-bound state and an inactive GDP-bound state; these states are regulated by two distinct families of proteins, guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). In this report, we studied the role of a previously uncharacterized GAP, ARHGAP18 (MacGAP). Overexpression of ARHGAP18 suppressed the activity of RhoA and disrupted stress fiber formation. Conversely, silencing of ARHGAP18 by siRNA transfection enhanced stress fiber formation and induced rounding of cells. We examined the role of ARHGAP18 in cell spreading and migration. Immunofluorescence analysis revealed that ARHGAP18 was localized to the leading edge during cell spreading and migration. ARGHAP18-knockdown cells showed impaired spreading, premature formation of stress fibers, and sustained activation of RhoA upon cell attachment. In addition, knockdown and overexpression of ARHGAP18 resulted in the inhibition and promotion of cell migration, respectively. Furthermore, ARHGAP18 was required for the polarization of cells for migration. Our results define ARHGAP18 as one of the crucial factors for the regulation of RhoA in order to control cell shape, spreading and migration. |
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Authors:
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Masao Maeda; Hitoki Hasegawa; Toshinori Hyodo; Satoko Ito; Eri Asano; Hong Yuang; Kohei Funasaka; Kaoru Shimokata; Yoshinori Hasegawa; Michinari Hamaguchi; Takeshi Senga |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-24 |
Journal Detail:
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Title: Molecular biology of the cell Volume: - ISSN: 1939-4586 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan Department of Biomedical Sciences, Chubu University, Kasugai, Aichi, Japan. |
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