ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape, spreading, and motility

Masao Maeda, Hitoki Hasegawa, Toshinori Hyodo, Satoko Ito, Eri Asano, Hong Yuang, Kohei Funasaka, Kaoru Shimokata, Yoshinori Hasegawa, Michinari Hamaguchi, Takeshi Senga

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


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 and GTPase-activating proteins (GAPs). 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 small interfering RNA 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. ARHGAP18-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 for the control of cell shape, spreading, and migration.

Original languageEnglish
Pages (from-to)3840-3852
Number of pages13
JournalMolecular Biology of the Cell
Issue number20
Publication statusPublished - 15-10-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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