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ZFIN ID: ZDB-PUB-141009-1
SNX13 reduction mediates heart failure through degradative sorting of apoptosis repressor with caspase recruitment domain
Li, J., Li, C., Zhang, D., Shi, D., Qi, M., Feng, J., Yuan, T., Xu, X., Liang, D., Xu, L., Zhang, H., Liu, Y., Chen, J., Ye, J., Jiang, W., Cui, Y., Zhang, Y., Peng, L., Zhou, Z., Chen, Y.H.
Date: 2014
Source: Nature communications 5: 5177 (Journal)
Registered Authors: Li, Jun
Keywords: none
MeSH Terms:
  • Animals
  • Apoptosis*
  • Apoptosis Regulatory Proteins/metabolism*
  • Caspase 8/metabolism
  • Disease Models, Animal
  • Heart Failure/metabolism*
  • Humans
  • Mice
  • Muscle Proteins/metabolism*
  • Myocytes, Cardiac/metabolism*
  • Sorting Nexins/metabolism*
  • Zebrafish
PubMed: 25295779 Full text @ Nat. Commun.
Heart failure (HF) is associated with complicated molecular remodelling within cardiomyocytes; however, the mechanisms underlying this process remain unclear. Here we show that sorting nexin-13 (SNX13), a member of both the sorting nexin and the regulator of G protein signalling (RGS) protein families, is a potent mediator of HF. Decreased levels of SNX13 are observed in failing hearts of humans and of experimental animals. SNX13-deficient zebrafish recapitulate HF with striking cardiomyocyte apoptosis. Mechanistically, a reduction in SNX13 expression facilitates the degradative sorting of apoptosis repressor with caspase recruitment domain (ARC), which is a multifunctional inhibitor of apoptosis. Consequently, the apoptotic pathway is activated, resulting in the loss of cardiac cells and the dampening of cardiac function. The N-terminal PXA structure of SNX13 is responsible for mediating the endosomal trafficking of ARC. Thus, this study reveals that SNX13 profoundly affects cardiac performance through the SNX13-PXA-ARC-caspase signalling pathway.