title: LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration.
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.
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Kun-Yi
authors.initials: KY
authors.lastname: Chien
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lee
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan.
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan.|Genome Research Center, National Yang Ming University, Taipei 11221, Taiwan.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan pai@mail.cgu.edu.tw.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan.|Liver Research Center, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Pai
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000185:Actinin / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D010766:Phosphorylation; D022502:Stress Fibers / Q000378:metabolism / Q000502:physiology
chemical_list: D060588:LIM Domain Proteins; C000619716:LIMCH1 protein, human; D018994:Myosin Light Chains; D000185:Actinin; D024507:Nonmuscle Myosin Type IIA