First Author | Feng HZ | Year | 2013 |
Journal | Am J Physiol Cell Physiol | Volume | 304 |
Issue | 10 | Pages | C1002-12 |
PubMed ID | 23485711 | Mgi Jnum | J:197993 |
Mgi Id | MGI:5495069 | Doi | 10.1152/ajpcell.00005.2013 |
Citation | Feng HZ, et al. (2013) Localization and function of Xinalpha in mouse skeletal muscle. Am J Physiol Cell Physiol 304(10):C1002-12 |
abstractText | 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, Xinalpha (Xirp1) and Xinbeta (Xirp2), is present in mammals. Ablation of the mouse Xinalpha (mXinalpha) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXinalpha and mXinbeta are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXinalpha in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXinalpha but not mXinbeta was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXinalpha with talin, vinculin, and filamin, but not beta-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXinalpha with vinculin. Loss of mXinalpha in mXinalpha-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXinalpha-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXinalpha 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 mXinalpha-null EDL muscle. The results suggest that mXinalpha play a role in MTJ conductance of contractile and stretching forces. |