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General Comment |
Dystrophin glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Morikawa Y et al. (2017) The regenerative capacity of the adult mammalian heart is limited because of the reduced ability of cardiomyocytes (CMs) to progress through mitosis(1). The regenerative capacity of endogenous CMs exists at birth but is lost postnatally, with subsequent organ growth occurring through CM hypertrophy(2,3). The Hippo pathway, a conserved kinase cascade, inhibits CM proliferation in the developing heart to control heart size and in the adult heart to prevent regeneration(4,5). The dystrophin glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for CM homeostasis. DGC deficiency in humans results in muscular dystrophy, including lethal Duchenne muscular dystrophy (DMD). We found that the DGC component dystroglycan 1 (DAG1) directly binds to Hippo pathway effector Yap to inhibit CM proliferation. The Yap-DAG1 interaction was enhanced by Hippo-induced Yap phosphorylation, revealing a connection between Hippo pathway function and the DGC. After injury, Hippo-deficient postnatal hearts maintained organ size control by repairing the defect with correct dimensions, whereas postnatal hearts doubly deficient for Hippo and the DGC showed CM overproliferation at the injury site. In mature Mdx mouse hearts-a model of DMD-Hippo deficiency protected against overload-induced heart failure.//////////////////
NCBI Summary:
This gene encodes the epsilon member of the sarcoglycan family. Sarcoglycans are transmembrane proteins that are components of the dystrophin-glycoprotein complex, which link the actin cytoskeleton to the extracellular matrix. Unlike other family members which are predominantly expressed in striated muscle, the epsilon sarcoglycan is more broadly expressed. Mutations in this gene are associated with myoclonus-dystonia syndrome. This gene is imprinted, with preferential expression from the paternal allele. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A pseudogene associated with this gene is located on chromosome 2. [provided by RefSeq, Oct 2016]
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