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Title: MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility

Abstract

Highlights: Black-Right-Pointing-Pointer MYBPH inhibits NMHC IIA assembly and cell motility. Black-Right-Pointing-Pointer MYBPH interacts to assembly-competent NM IIA. Black-Right-Pointing-Pointer MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA. -- Abstract: Actomyosin filament assembly is a critical step in tumor cell migration. We previously found that myosin binding protein H (MYBPH) is directly transactivated by the TTF-1 lineage-survival oncogene in lung adenocarcinomas and inhibits phosphorylation of the myosin regulatory light chain (RLC) of non-muscle myosin IIA (NM IIA) via direct interaction with Rho kinase 1 (ROCK1). Here, we report that MYBPH also directly interacts with an additional molecule, non-muscle myosin heavy chain IIA (NMHC IIA), which was found to occur between MYBPH and the rod portion of NMHC IIA. MYBPH inhibited NMHC IIA assembly and reduced cell motility. Conversely, siMYBPH-induced increased motility was partially, yet significantly, suppressed by blebbistatin, a non-muscle myosin II inhibitor, while more profound effects were attained by combined treatment with siROCK1 and blebbistatin. Electron microscopy observations showed well-ordered paracrystals of NMHC IIA reflecting an assembled state, which were significantly less frequently observed in the presence of MYBPH. Furthermore, an in vitro sedimentation assay showed that a greater amount of NMHC IIA was in an unassembled statemore » in the presence of MYBPH. Interestingly, treatment with a ROCK inhibitor that impairs transition of NM IIA from an assembly-incompetent to assembly-competent state reduced the interaction between MYBPH and NMHC IIA, suggesting that MYBPH has higher affinity to assembly-competent NM IIA. These results suggest that MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA, and negatively regulates actomyosin organization at 2 distinct steps, resulting in firm inhibition of NM IIA assembly.« less

Authors:
 [1];  [2]; ; ;  [1];  [1]
  1. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550 (Japan)
  2. Division of Integrated Project, EcoTopia Science Institute, Nagoya University, Chikusa-ku, Nagoya 464-8603 (Japan)
Publication Date:
OSTI Identifier:
22210327
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 428; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; ELECTRON MICROSCOPY; IN VITRO; INHIBITION; LUNGS; MUSCLES; MYOSIN; ONCOGENES; PHOSPHORYLATION; TUMOR CELLS

Citation Formats

Hosono, Yasuyuki, Usukura, Jiro, Yamaguchi, Tomoya, Yanagisawa, Kiyoshi, Suzuki, Motoshi, and Takahashi, Takashi, E-mail: tak@med.nagoya-u.ac.jp. MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.10.036.
Hosono, Yasuyuki, Usukura, Jiro, Yamaguchi, Tomoya, Yanagisawa, Kiyoshi, Suzuki, Motoshi, & Takahashi, Takashi, E-mail: tak@med.nagoya-u.ac.jp. MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility. United States. doi:10.1016/J.BBRC.2012.10.036.
Hosono, Yasuyuki, Usukura, Jiro, Yamaguchi, Tomoya, Yanagisawa, Kiyoshi, Suzuki, Motoshi, and Takahashi, Takashi, E-mail: tak@med.nagoya-u.ac.jp. Fri . "MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility". United States. doi:10.1016/J.BBRC.2012.10.036.
@article{osti_22210327,
title = {MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility},
author = {Hosono, Yasuyuki and Usukura, Jiro and Yamaguchi, Tomoya and Yanagisawa, Kiyoshi and Suzuki, Motoshi and Takahashi, Takashi, E-mail: tak@med.nagoya-u.ac.jp},
abstractNote = {Highlights: Black-Right-Pointing-Pointer MYBPH inhibits NMHC IIA assembly and cell motility. Black-Right-Pointing-Pointer MYBPH interacts to assembly-competent NM IIA. Black-Right-Pointing-Pointer MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA. -- Abstract: Actomyosin filament assembly is a critical step in tumor cell migration. We previously found that myosin binding protein H (MYBPH) is directly transactivated by the TTF-1 lineage-survival oncogene in lung adenocarcinomas and inhibits phosphorylation of the myosin regulatory light chain (RLC) of non-muscle myosin IIA (NM IIA) via direct interaction with Rho kinase 1 (ROCK1). Here, we report that MYBPH also directly interacts with an additional molecule, non-muscle myosin heavy chain IIA (NMHC IIA), which was found to occur between MYBPH and the rod portion of NMHC IIA. MYBPH inhibited NMHC IIA assembly and reduced cell motility. Conversely, siMYBPH-induced increased motility was partially, yet significantly, suppressed by blebbistatin, a non-muscle myosin II inhibitor, while more profound effects were attained by combined treatment with siROCK1 and blebbistatin. Electron microscopy observations showed well-ordered paracrystals of NMHC IIA reflecting an assembled state, which were significantly less frequently observed in the presence of MYBPH. Furthermore, an in vitro sedimentation assay showed that a greater amount of NMHC IIA was in an unassembled state in the presence of MYBPH. Interestingly, treatment with a ROCK inhibitor that impairs transition of NM IIA from an assembly-incompetent to assembly-competent state reduced the interaction between MYBPH and NMHC IIA, suggesting that MYBPH has higher affinity to assembly-competent NM IIA. These results suggest that MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA, and negatively regulates actomyosin organization at 2 distinct steps, resulting in firm inhibition of NM IIA assembly.},
doi = {10.1016/J.BBRC.2012.10.036},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 428,
place = {United States},
year = {2012},
month = {11}
}