LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2
Phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulates at the leading edge of migrating cells and works, at least partially, as both a compass to indicate directionality and a hub for subsequent intracellular events. However, how PtdIns(3,4,5)P3 regulates the migratory machinery has n...
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American Society for Biochemistry and Molecular Biology Inc.
2010
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my.iium.irep.124442011-12-23T11:01:50Z http://irep.iium.edu.my/12444/ LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 Takabayashi, Tetsuji Xie, Min-Jue Takeuchi, Seiji Kawasaki, Motomi Yagi, Hideshi Okamoto, Masayuki Rahman, Mohammad Tariqur Malik, Fawzia Kuroda, Kazuki Kubota, Chikara Fujieda, Shigeharu Nagano, Takashi Sato, Makoto RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulates at the leading edge of migrating cells and works, at least partially, as both a compass to indicate directionality and a hub for subsequent intracellular events. However, how PtdIns(3,4,5)P3 regulates the migratory machinery has not been fully elucidated. Here, we demonstrate a novel mechanism for efficient lamellipodium formation that depends on PtdIns(3,4,5)P3 and the reciprocal regulation of PtdIns(3,4,5)P3 itself. LL5β, whose subcellular localization is directed by membrane PtdIns(3,4,5)P3, recruits the actin-cross-linking protein Filamin A to the plasma membrane, where PtdIns(3,4,5)P3 accumulates, with the Filamin A-binding Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2). A large and dynamic lamellipodium was formed in the presence of Filamin A and LL5β by the application of epidermal growth factor. Conversely, depletion of either Filamin A or LL5β or the overexpression of either an F-actin-cross-linking mutant of Filamin A or a mutant of LL5β without its PtdIns(3,4,5)P3-interacting region inhibited such events in COS-7 cells. Because F-actin initially polymerizes near the plasma membrane, it is likely that membrane-recruited Filamin A efficiently cross-links newly polymerized F-actin, leading to enhanced lamellipodium formation at the site of PtdIns(3,4,5)P3 accumulation. Moreover, we demonstrate that co-recruited SHIP2 dephosphorylates PtdIns(3,4,5)P3 at the same location. American Society for Biochemistry and Molecular Biology Inc. 2010 Article REM application/pdf en http://irep.iium.edu.my/12444/1/LL5B_Direct_the_translocation_of_filamin_A_sites.pdf Takabayashi, Tetsuji and Xie, Min-Jue and Takeuchi, Seiji and Kawasaki, Motomi and Yagi, Hideshi and Okamoto, Masayuki and Rahman, Mohammad Tariqur and Malik, Fawzia and Kuroda, Kazuki and Kubota, Chikara and Fujieda, Shigeharu and Nagano, Takashi and Sato, Makoto (2010) LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2. Journal of Biological Chemistry, 285 (21). pp. 16155-16165. ISSN 0021-9258 (P), 1083-351X (O) http://dx.doi.org/10.1074/jbc.M109.081901 10.1074/jbc.M109.081901 |
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RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Takabayashi, Tetsuji Xie, Min-Jue Takeuchi, Seiji Kawasaki, Motomi Yagi, Hideshi Okamoto, Masayuki Rahman, Mohammad Tariqur Malik, Fawzia Kuroda, Kazuki Kubota, Chikara Fujieda, Shigeharu Nagano, Takashi Sato, Makoto LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
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Phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulates at the leading edge of migrating cells and works, at least partially, as both a compass to indicate directionality and a hub for subsequent intracellular events. However, how PtdIns(3,4,5)P3 regulates the migratory machinery has not been fully elucidated. Here, we demonstrate a novel mechanism for efficient lamellipodium formation that depends on PtdIns(3,4,5)P3 and the reciprocal regulation of PtdIns(3,4,5)P3 itself. LL5β, whose subcellular localization is directed by membrane PtdIns(3,4,5)P3, recruits the actin-cross-linking protein Filamin A to the plasma membrane, where PtdIns(3,4,5)P3 accumulates, with the Filamin A-binding Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2). A large and dynamic lamellipodium was formed in the presence of Filamin A and LL5β by the application of epidermal growth factor. Conversely, depletion of either Filamin A or LL5β or the overexpression of either an F-actin-cross-linking mutant of Filamin A or a mutant of LL5β without its PtdIns(3,4,5)P3-interacting region inhibited such events in COS-7 cells. Because F-actin initially polymerizes near the plasma membrane, it is likely that membrane-recruited Filamin A efficiently cross-links newly polymerized F-actin, leading to enhanced lamellipodium formation at the site of PtdIns(3,4,5)P3 accumulation. Moreover, we demonstrate that co-recruited SHIP2 dephosphorylates PtdIns(3,4,5)P3 at the same location. |
format |
Article |
author |
Takabayashi, Tetsuji Xie, Min-Jue Takeuchi, Seiji Kawasaki, Motomi Yagi, Hideshi Okamoto, Masayuki Rahman, Mohammad Tariqur Malik, Fawzia Kuroda, Kazuki Kubota, Chikara Fujieda, Shigeharu Nagano, Takashi Sato, Makoto |
author_facet |
Takabayashi, Tetsuji Xie, Min-Jue Takeuchi, Seiji Kawasaki, Motomi Yagi, Hideshi Okamoto, Masayuki Rahman, Mohammad Tariqur Malik, Fawzia Kuroda, Kazuki Kubota, Chikara Fujieda, Shigeharu Nagano, Takashi Sato, Makoto |
author_sort |
Takabayashi, Tetsuji |
title |
LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
title_short |
LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
title_full |
LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
title_fullStr |
LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
title_full_unstemmed |
LL5 directs the translocation of Filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2 |
title_sort |
ll5 directs the translocation of filamin a and ship2 to sites of phosphatidylinositol 3,4,5-triphosphate (ptdins(3,4,5)p3) accumulation, and ptdins(3,4,5)p3 localization is mutually modified by co-recruited ship2 |
publisher |
American Society for Biochemistry and Molecular Biology Inc. |
publishDate |
2010 |
url |
http://irep.iium.edu.my/12444/1/LL5B_Direct_the_translocation_of_filamin_A_sites.pdf http://irep.iium.edu.my/12444/ http://dx.doi.org/10.1074/jbc.M109.081901 |
_version_ |
1643606621688954880 |
score |
13.222552 |