title: Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.
abstract: The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.
authors.affiliation: Muscle Development Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vlahovich
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kee
authors.forename: Chris
authors.initials: C
authors.lastname: Van der Poel
authors.forename: Emma
authors.initials: E
authors.lastname: Kettle
authors.forename: Delia
authors.initials: D
authors.lastname: Hernandez-Deviez
authors.forename: Christine
authors.initials: C
authors.lastname: Lucas
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D020033:Protein Isoforms; C411923:Tpm3 protein, mouse; D014335:Tropomyosin