Changes in CLIMP63 expression alter the organization of the microtubule network of mouse skeletal muscle fibers

The endoplasmic reticulum (ER) is a highly specialized organelle, responsible for protein synthesis and Ca2+ handling. It establishes contacts with several other organelles and is closely associated with microtubules (MTs). MTs act as a scaffold for ER positioning and remodeling, playing a central role in ER morphogenesis. In skeletal muscle, the sarcoplasmic reticulum (SR) is a specialization of the ER, dedicated to Ca2+ storage and release necessary for muscle contraction. Recent data suggested that the SR protein triadin is involved in MT-dependent organization of SR membranes by interacting with the cytoskeleton-linking membrane protein 63 (CLIMP63), an ER/SR-shaping protein able to bind MTs. Research conducted in our laboratories identified CLIMP63 as an interactor of two additional SR proteins, junctophilin 1 and 2. To further evaluate the role of CLIMP63 on the SR and MT organization, we performed experiments of either overexpression or downregulation of CLIMP63 in skeletal muscles from newborn and adult mice. While we found that neither overexpression nor downregulation of CLIMP63 significantly altered the organization of the SR, the analysis of MT organization highlighted that changes in CLIMP63 expression alter the architecture of the MT network, suggesting a role of this protein in the structural organization of MTs in skeletal muscle.