4.8 Article

Myosin X is a downstream effector of PI(3)K during phagocytosis

Journal

NATURE CELL BIOLOGY
Volume 4, Issue 7, Pages 469-477

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ncb805

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Funding

  1. NHLBI NIH HHS [HL54164] Funding Source: Medline
  2. NIAMS NIH HHS [K01 AR02158, K01 AR002158] Funding Source: Medline
  3. NIDCD NIH HHS [R29 DC003299, DC03299] Funding Source: Medline

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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.

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