MG29 Interacts with Bin‐1 to Maintain T‐Tubule Structure in Skeletal Muscle Physiology and Regeneration

Abstract

Mitsugumin 29 (MG29), a member of the synaptophysin‐like family proteins, is a transmembrane protein primarily expressed in the t‐tubule membranes of skeletal muscle. In the current study we have found that t‐tubules in skeletal muscle of mg29−/− have defective morphology, indicating importance of MG29 in maintenance of muscle structure and function. To elucidate the role of MG29 in muscle physiology, we performed two‐color STORM super‐resolution imaging analysis confirmed co‐localization of MG29 and Bin‐1 on t‐tubules of skeletal muscle. We also performed co‐immunoprecipitation and found that MG29 can bind to Bin‐1, another t‐tubular protein. Recombinant MG29 protein domain fragments tagged with GST were expressed and Bin‐1 was found to bind to the cytosolic domains of MG29. Furthermore, organized distribution of Bin‐1 is severely disrupted in mg29−/− muscle. To test the function of MG29 in muscle regeneration, we injured gastrocnemius muscle with cardiotoxin (CTX) and tracked muscle repair and regeneration. Western blot showed that following CTX injury, MG29 protein levels were transiently reduced from day 1 to day 3, followed by recovery associated with muscle regeneration by day 5. Protein level of Bin‐1 in wild type muscle was also reduced upon CTX‐injury and increased during the recovery process. Compared with wild type muscle, the mg29−/− muscle displayed delayed regeneration and increased fibrosis following CTX‐induced injury. Together our data suggest that functional interaction between MG29 and Bin‐1 contribute to maintenance and formation of t‐tubule network while playing a role in muscle regeneration and regeneration. Targeting this MG29‐Bin‐1 interaction might provide a potential effective approach for treatment of muscle diseasesSupport or Funding InformationThis work was supported by grants from the National Institutes of Health (NIH) (AR067766 and HL124122)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.