title: Gene duplication and conversion events shaped three homologous, differentially expressed myosin regulatory light chain (MLC2) genes.
abstract: Myosin II is a hexameric protein complex consisting of two myosin heavy chains, two myosin essential light chains and two myosin regulatory light chains. Multiple subunit isoforms exist, allowing great diversity in myosin II composition which likely impacts on its contractile properties. Little is known about the evolutionary origin, expression pattern and function of myosin regulatory light chain (MLC2) isoforms. We analysed the evolutionary relationship between smooth muscle (sm), nonmuscle (nm) and nonmuscle-like (nml) MLC2 genes, which encode three homologous proteins expressed in nonmuscle cells. The three genes arose by successive gene duplication events. The high sequence similarity between the tandemly arranged nm- and nml-MLC2 genes is best explained by gene conversion. Urea/glycerol-polyacrylamide gel electrophoresis and RNA analysis were employed to monitor expression of sm-, nm- and nml-MLC2 in human and mouse cell lines. Conspicuous differences between transformed and non-transformed cells were observed, with sm-MLC2 being suppressed in Ras-transformed cells. Our findings shed light on the evolutionary history of three homologous MLC2 proteins and point to isoform-specific cell growth-related roles in nonmuscle cell myosin II contractility.
authors.affiliation: Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lieke
authors.initials: L
authors.lastname: Gerrits
authors.forename: Gijs J
authors.initials: GJ
authors.lastname: Overheul
authors.forename: Ronny C
authors.initials: RC
authors.lastname: Derks
authors.forename: Bé
authors.initials: B
authors.lastname: Wieringa
authors.forename: Wiljan J A J
authors.initials: WJ
authors.lastname: Hendriks
authors.forename: Derick G
authors.initials: DG
authors.lastname: Wansink
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D024722:Cardiac Myosins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D019143:Evolution, Molecular; D005785:Gene Conversion; D020440:Gene Duplication; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018994:Myosin Light Chains / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C521958:Mylpf protein, mouse; D018994:Myosin Light Chains; D020033:Protein Isoforms; C107184:myosin light chain 2; D024722:Cardiac Myosins