title: Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle.
abstract: Tropomodulin (E-Tmod) is an actin filament pointed end capping protein that maintains the length of the sarcomeric actin filaments in striated muscle. Here, we describe the identification and characterization of a novel tropomodulin isoform, skeletal tropomodulin (Sk-Tmod) from chickens. Sk-Tmod is 62% identical in amino acid sequence to the previously described chicken E-Tmod and is the product of a different gene. Sk-Tmod isoform sequences are highly conserved across vertebrates and constitute an independent group in the tropomodulin family. In vitro, chicken Sk-Tmod caps actin and tropomyosin-actin filament pointed ends to the same extent as does chicken E-Tmod. However, E- and Sk-Tmods differ in their tissue distribution; Sk-Tmod predominates in fast skeletal muscle fibers, lens, and erythrocytes, while E-Tmod is found in heart and slow skeletal muscle fibers. Additionally, their expression is developmentally regulated during chicken breast muscle differentiation with Sk-Tmod replacing E-Tmod after hatching. Finally, in skeletal muscle fibers that coexpress both Sk- and E-Tmod, they are recruited to different actin filament-containing cytoskeletal structures within the cell: myofibrils and costameres, respectively. All together, these observations support the hypothesis that vertebrates have acquired different tropomodulin isoforms that play distinct roles in vivo.
authors.affiliation: Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: A
authors.initials: A
authors.lastname: Almenar-Queralt
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: C A
authors.initials: CA
authors.lastname: Conley
authors.forename: L
authors.initials: L
authors.lastname: Ribas de Pouplana
authors.forename: V M
authors.initials: VM
authors.lastname: Fowler
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens; D018076:DNA, Complementary; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000378:metabolism; D051348:Tropomodulin
chemical_list: D000199:Actins; D002352:Carrier Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D020033:Protein Isoforms; C495839:TMOD4 protein, human; D051348:Tropomodulin; D013049:Spectrin