title: Nonmuscle myosin IIA is required for lamellipodia formation through binding to WAVE2 and phosphatidylinositol 3,4,5-triphosphate.
abstract: Investigation of the mechanism underlying cell membrane-targeted WAVE2 capture by phosphatidylinositol 3,4,5-triphosphate (PIP(3)) through IRSp53 revealed an unidentified 250-kDa protein (p250) bound to PIP(3). We identified p250 as nonmuscle myosin IIA heavy chain (MYH9) by mass spectrometry and immunoblot analysis using anti-MYH9 antibody. After stimulation with insulin-like growth factor I (IGF-I), MYH9 colocalized with PIP(3) in lamellipodia at the leading edge of cells. Depletion of MYH9 expression by small interfering RNA (siRNA) and inhibition of myosin II activity by blebbistatin abrogated the formation of actin filament (F-actin) arcs and lamellipodia induced by IGF-I. MYH9 was constitutively associated with WAVE2, which was dependent on myosin II activity, and the MYH9-WAVE2 complex colocalized to PIP(3) at the leading edge after IGF-I stimulation. These results indicate that MYH9 is required for lamellipodia formation since it provides contractile forces and tension for the F-actin network to form convex arcs at the leading edge through constitutive binding to WAVE2 and colocalization with PIP(3) in response to IGF-I.
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, Yokohama 241-0815, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morimura
authors.forename: Katsuo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000199:Actins / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011554:Pseudopodia / Q000502:physiology*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
chemical_list: D000199:Actins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018129:Phosphatidylinositol Phosphates; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C060974:phosphatidylinositol 3,4,5-triphosphate; D007334:Insulin-Like Growth Factor I; D018995:Myosin Heavy Chains