Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle

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 tropo modulin 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 tropomyos in-actin filament pointed ends to the same extent as does chicken E-Tmod, H owever, E- and Sk-Tmods differ in their tissue distribution; Sk-Tmod predom inates in fast skeletal muscle fibers, lens, and erythrocytes, while E-Tmod is found in heart and slow skeletal muscle fibers. Additionally, their exp ression is developmentally regulated during chicken breast muscle different iation with Sk-Tmod replacing E-Tmod after hatching. Finally, in skeletal m uscle fibers that coexpress both Sk- and E-Tmod, they are recruited to diff erent actin filament-containing cytoskeletal structures within the cell: my ofibrils and costameres, respectively. All together, these observations sup port the hypothesis that vertebrates have acquired different tropomodulin i soforms that play distinct roles in vivo.