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Regulation of myonuclear positioning and muscle function by the skeletal muscle-specific CIP protein

Jianming Liu, Zhan-Peng Huang, Mao Nie, Gang Wang, William J. Silva, Qiumei Yang, Paula Paccielli Freire, Xiaoyun Hu, Huaqun Chen, Zhong‐Liang Deng, William T. Pu, Da‐Zhi Wang

2020Proceedings of the National Academy of Sciences58 citationsDOIOpen Access PDF

Abstract

Significance The arrangement of nuclei in myofibers, which are multinucleated skeletal muscle cells, is essential for their proper function. Abnormal nuclear positioning in myofibers is a common feature of several skeletal muscle diseases, including centronuclear myopathy and muscular dystrophy. Here, we show an isoform of the CIP protein (sk-CIP) contributes to the regulation of the positioning of nuclei in myofibers by interacting with both the LINC complex (Linker of Nucleoskeleton and Cytoskeleton) and proteins in the microtubule-organizing center (MTOC). Through these interactions, sk-CIP appears to function as a skeletal muscle-specific anchoring protein that regulates nuclear positioning in myofibers. Further investigation and understanding of myofiber nuclear positioning may facilitate the development of novel therapies for some diseases of skeletal muscle.

Topics & Concepts

Skeletal muscleMultinucleateMyocyteCell biologyITGA7BiologyMuscular dystrophyGene isoformMicrotubule organizing centerMicrotubuleCytoskeletonMyopathyNuclear proteinFunction (biology)AnatomyCellCentrosomeGeneticsGeneTranscription factorCell cycleMuscle Physiology and DisordersNuclear Structure and FunctionNeurogenetic and Muscular Disorders Research