title: Myosin motor isoforms direct specification of actomyosin function by tropomyosins.
abstract: Myosins and tropomyosins represent two cytoskeletal proteins that often work together with actin filaments in contractile and motile cellular processes. While the specialized role of tropomyosin in striated muscle myosin-II regulation is well characterized, its role in nonmuscle myosin regulation is poorly understood. We previously showed that fission yeast tropomyosin (Cdc8p) positively regulates myosin-II (Myo2p) and myosin-V (Myo52p) motors. To understand the broader implications of this regulation we examined the role of two mammalian tropomyosins (Tpm3.1cy/Tm5NM1 and Tpm4.2cy/Tm4) recently implicated in cancer cell proliferation and metastasis. Like Cdc8p, the Tpm3.1cy and Tpm4.2cy isoforms significantly enhance Myo2p and Myo52p motor activity, converting nonprocessive Myo52p molecules into processive motors that can walk along actin tracks as single molecules. In contrast to the positive regulation of Myo2p and Myo52p, Cdc8p and the mammalian tropomyosins potently inhibited skeletal muscle myosin-II, while having negligible effects on the highly processive mammalian myosin-Va. In support of a conserved role for certain tropomyosins in regulating nonmuscle actomyosin structures, Tpm3.1cy supported normal contractile ring function in fission yeast. Our work reveals that actomyosin regulation by tropomyosin is dependent on the myosin isoform, highlighting a general role for specific isoforms of tropomyosin in sorting myosin motor outputs.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Clayton
authors.forename: Luther W
authors.initials: LW
authors.lastname: Pollard
authors.forename: George G
authors.initials: GG
authors.lastname: Murray
authors.forename: Matthew
authors.initials: M
authors.lastname: Lord
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D020409:Molecular Motor Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D014335:Tropomyosin / Q000378:metabolism*
chemical_list: C410737:Cdc8 protein, S pombe; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D020409:Molecular Motor Proteins; D020033:Protein Isoforms; D029702:Schizosaccharomyces pombe Proteins; D014335:Tropomyosin; D049452:Green Fluorescent Proteins; C077511:MYO5A protein, human; D000205:Actomyosin; C554097:Myo52 protein, S pombe; D000251:Adenosine Triphosphatases; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D009218:Myosins
keywords: actin; motor sorting; myosin isoforms; regulation; tropomyosin isoforms