The PDZ-Containing Unconventional Myosin XVIIIA Regulates Embryonic Muscle Integrity in Zebrafish  

作　　者：Jianmeng Cao Shangqi Li Ming Shao Xiaoning Cheng Zhigang Xu Deli Shi 

机构地区：[1]School of Life Sciences,Shandong University [2]Sorbonne Universite's,UPMC Univ Paris 06,UMR 7622,Laboratory of Developmental Biology,F-75005 Paris,France [3]CNRS,UMR 7622,Laboratory of Developmental Biology,F-75005 Paris,France

出　　处：《Journal of Genetics and Genomics》2014年第8期417-428,共12页遗传学报（英文版）

基　　金：supported by the grants from the National Science Foundation of China (No. 31271556);Association Francaise contre les Myopathies (AFM);the Agence Nationale de la Recherche (ANR-09-BLAN-0262-03) in France

摘　　要：Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.

关 键 词：Myosin XVIIIA MYO18A Unconventional myosin MYOFIBER MUSCLE DYSTROPHIN DYSTROGLYCAN ZEBRAFISH 

分 类 号：Q78[生物学—分子生物学]