Xin proteins and intercalated disc maturation, signaling and diseases.
Intercalated discs (ICDs) are cardiac-specific structures responsible for mechanical and electrical communication among adjacent cardiomyocytes and are implicated in signal transduction.  The striated muscle-specific Xin repeat-containing proteins localize to ICDs and play critical roles in ICD formation and cardiac function. Knocking down the Xin gene in chicken embryos collapses the wall of developing heart chambers and leads to abnormal cardiac morphogenesis. In mammals, a pair of paralogous genes, Xinalpha and Xinbeta exist. Ablation of the mouse Xinalpha (mXinalpha) does not affect heart development. Instead, mXinalpha-deficient mice show adult late-onset cardiac hypertrophy and cardiomyopathy with conduction defects. The mXinalpha-deficient hearts up-regulate mouse Xinbeta (mXinbeta, suggesting a partial compensatory role of mXinbeta. Complete loss of mXinbeta however, leads to failure of forming ICD, mis-localization of mXinalpha, and early postnatal lethality. In this review, we will briefly discuss recent advances in the anatomy and function of ICDs. We will then review what we know about Xin repeat-containing proteins and how this protein family promotes ICD maturation and stability for normal cardiac function.
Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
Qinchuan
Q
Wang
Jenny Li-Chun
JL
Lin
Kuo-Ho
KH
Wu
Da-Zhi
DZ
Wang
Rebecca S
RS
Reiter
Haley W
HW
Sinn
Cheng-I
CI
Lin
Chung-Jing J
CJ
Lin
D000818:Animals; D051177:Catenins / Q000378:metabolism; D002450:Cell Communication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D051177:Catenins; D004268:DNA-Binding Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051153:Wnt Proteins; C512114:XIRP1 protein, human; C118478:Xin protein, mouse