2. Academic Validation
  3. LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration

LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration

  • Mol Biol Cell. 2017 Apr 15;28(8):1054-1065. doi: 10.1091/mbc.E15-04-0218.
Yu-Hung Lin 1,  Yen-Yi Zhen 2,  Kun-Yi Chien 1 2,  I-Ching Lee 1,  Wei-Chi Lin 3,  Mei-Yu Chen 3 4,  Li-Mei Pai 5 2 6
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
  • 2 Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan.
  • 3 Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan.
  • 4 Genome Research Center, National Yang Ming University, Taipei 11221, Taiwan.
  • 5 Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan [email protected].
  • 6 Liver Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan.
PMID: 28228547 DOI: 10.1091/mbc.E15-04-0218
Abstract

Nonmuscle Myosin II (NM-II) is an important motor protein involved in cell migration. Incorporation of NM-II into actin stress fiber provides a traction force to promote actin retrograde flow and focal adhesion assembly. However, the components involved in regulation of NM-II activity are not well understood. Here we identified a novel actin stress fiber-associated protein, LIM and calponin-homology domains 1 (LIMCH1), which regulates NM-II activity. The recruitment of LIMCH1 into contractile stress fibers revealed its localization complementary to actinin-1. LIMCH1 interacted with NM-IIA, but not NM-IIB, independent of the inhibition of Myosin ATPase activity with blebbistatin. Moreover, the N-terminus of LIMCH1 binds to the head region of NM-IIA. Depletion of LIMCH1 attenuated Myosin regulatory LIGHT chain (MRLC) diphosphorylation in HeLa cells, which was restored by reexpression of small interfering RNA-resistant LIMCH1. In addition, LIMCH1-depleted HeLa cells exhibited a decrease in the number of actin stress fibers and focal adhesions, leading to enhanced cell migration. Collectively, our data suggest that LIMCH1 plays a positive role in regulation of NM-II activity through effects on MRLC during cell migration.

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