Myosin X is a downstream effector of PI(3)K during phagocytosis.
Phagocytosis is a phosphatidylinositol-3-OH-kinase (PI(3)K)-dependent process in macrophages. We identified Myo10 (Myosin-X), an unconventional myosin with pleckstrin homology (PH) domains, as a potential downstream target of PI(3)K. Myo10 was recruited to phagocytic cups in a wortmannin-sensitive manner. Expression of a truncation construct of Myo10 (Myo10 tail) in a macrophage cell line or cytosolic loading of anti-Myo10 antibodies in bovine alveolar macrophages inhibited phagocytosis. In contrast, expression of a Myo10 tail construct containing a point mutation in one of its PH domains failed to inhibit phagocytosis. Expression of Myo10 tail inhibited spreading, but not adhesion, on IgG-coated substrates, consistent with a function for Myo10 in pseudopod extension. We propose that Myo10 provides a molecular link between PI(3)K and pseudopod extension during phagocytosis.
Cox
Dianne
D
Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Berg
Jonathan S
JS
Cammer
Michael
M
Chinegwundoh
John O
JO
Dale
Benjamin M
BM
Cheney
Richard E
RE
Greenberg
Steven
S
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002460:Cell Line; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009218:Myosins / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017354:Point Mutation; D011554:Pseudopodia / Q000502:physiology; D013329:Structure-Activity Relationship; D000077191:Wortmannin
D000730:Androstadienes; C409064:Myo10 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D009218:Myosins; D000077191:Wortmannin