BetaPIX and GIT1 regulate HGF-induced lamellipodia formation and WAVE2 transport.
Formation of lamellipodia is the first step during cell migration, and involves actin reassembly at the leading edge of migrating cells through the membrane transport of WAVE2. However, the factors that regulate WAVE2 transport to the cell periphery for initiating lamellipodia formation have not been elucidated. We report here that in human breast cancer MDA-MB-231 cells, the hepatocyte growth factor (HGF) induced the association between the constitutive complex of betaPIX and GIT1 with WAVE2, which was concomitant with the induction of lamellipodia formation and WAVE2 transport. Although depletion of betaPIX by RNA interference abrogated the HGF-induced WAVE2 transport and lamellipodia formation, GIT1 depletion caused HGF-independent WAVE2 transport and lamellipodia formation. Collectively, we suggest that betaPIX releases cells from the GIT1-mediated suppression of HGF-independent responses and recruits GIT1 to WAVE2, thereby facilitating HGF-induced WAVE2 transport and lamellipodia formation.
Morimura
Shigeru
S
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan. smorimur@gancen.asahi.yokohama.jp
Suzuki
Katsuo
K
Takahashi
Kazuhide
K
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology*; D064067:Rho Guanine Nucleotide Exchange Factors; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; D020662:Guanine Nucleotide Exchange Factors; C066855:HGF protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D017228:Hepatocyte Growth Factor