title: Localization and function of Xinα in mouse skeletal muscle.
abstract: The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xinα (Xirp1) and Xinβ (Xirp2), is present in mammals. Ablation of the mouse Xinα (mXinα) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXinα and mXinβ are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXinα in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXinα but not mXinβ was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXinα with talin, vinculin, and filamin, but not β-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXinα with vinculin. Loss of mXinα in mXinα-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXinα-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXinα exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXinα-null EDL muscle. The results suggest that mXinα play a role in MTJ conductance of contractile and stretching forces.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Wang
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Reiter
authors.forename: Jenny L-C
authors.initials: JL
authors.lastname: Lin
authors.forename: Jim J-C
authors.initials: JJ
authors.lastname: Lin
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D001808:Blood Vessels; D006332:Cardiomegaly / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003964:Diaphragm / Q000473:pathology; D064448:Filamins; D060588:LIM Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular; D009206:Myocardium / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016608:Talin / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C572128:CMYA1 protein, mouse; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D064448:Filamins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D016608:Talin; D020107:Troponin T; C500305:XIRP2 protein, mouse; D051176:beta Catenin; D016596:Vinculin
keywords: Xinα; fast troponin T fragmentation; muscle fatigue; myotendinous junction