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

被引:165
作者
Cox, D
Berg, JS
Cammer, M
Chinegwundoh, JO
Dale, BM
Cheney, RE
Greenberg, S
机构
[1] Columbia Univ, Dept Med, New York, NY 10032 USA
[2] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA
[3] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA
[4] Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA
关键词
D O I
10.1038/ncb805
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:469 / 477
页数:9
相关论文
共 49 条
  • [1] A ROLE FOR MARCKS, THE ALPHA-ISOZYME OF PROTEIN-KINASE-C AND MYOSIN-I IN ZYMOSAN PHAGOCYTOSIS BY MACROPHAGES
    ALLEN, LAH
    ADEREM, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) : 829 - 840
  • [2] A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages
    Araki, N
    Johnson, MT
    Swanson, JA
    [J]. JOURNAL OF CELL BIOLOGY, 1996, 135 (05) : 1249 - 1260
  • [3] Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation
    Bajno, L
    Peng, XR
    Schreiber, AD
    Moore, HP
    Trimble, WS
    Grinstein, S
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 149 (03) : 697 - 705
  • [4] Berg JS, 2000, J CELL SCI, V113, P3439
  • [5] A millennial myosin census
    Berg, JS
    Powell, BC
    Cheney, RE
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (04) : 780 - 794
  • [6] Myosin-X is an unconventional myosin that undergoes intrafilopodial motility
    Berg, JS
    Cheney, RE
    [J]. NATURE CELL BIOLOGY, 2002, 4 (03) : 246 - 250
  • [7] Inactivation of two Dictyostelium discoideum genes, DdPIK1 and DdPIK2, encoding proteins related to mammalian phosphatidylinositide 3-kinases, results in defects in endocytosis, lysosome to postlysosome transport, and actin cytoskeleton organization
    Buczynski, G
    Grove, B
    Nomura, A
    Kleve, M
    Bush, J
    Firtel, RA
    Cardelli, J
    [J]. JOURNAL OF CELL BIOLOGY, 1997, 136 (06) : 1271 - 1286
  • [8] Myosin-VIIb, a novel unconventional myosin, is a constituent of microvilli in transporting epithelia
    Chen, ZY
    Hasson, T
    Zhang, DS
    Schwender, BJ
    Derfler, BH
    Mooseker, MS
    Corey, DP
    [J]. GENOMICS, 2001, 72 (03) : 285 - 296
  • [9] The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane
    Chishti, AH
    Kim, AC
    Marfatia, SM
    Lutchman, M
    Hanspal, M
    Jindal, H
    Liu, SC
    Low, PS
    Rouleau, GA
    Mohandas, N
    Chasis, JA
    Conboy, JG
    Gascard, P
    Takakuwa, Y
    Huang, SC
    Benz, EJ
    Bretscher, A
    Fehon, RG
    Gusella, AF
    Ramesh, V
    Solomon, F
    Marchesi, VT
    Tsukita, S
    Tsukita, S
    Arpin, M
    Louvard, D
    Tonks, NK
    Anderson, JM
    Fanning, AS
    Bryant, PJ
    Woods, DF
    Hoover, KB
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (08) : 281 - 282
  • [10] Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes
    Cox, D
    Chang, P
    Zhang, Q
    Reddy, PG
    Bokoch, GM
    Greenberg, S
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (09) : 1487 - 1494