CCAR-1 affects hemidesmosome biogenesis by regulating unc-52 /perlecan alternative splicing in the C. elegans epidermis

Journal of Cell Science
Rong FuHuimin Zhang

Abstract

Hemidesmosomes are epithelial-specific attachment structures that maintain tissue integrity and resist tension. Despite their importance, how hemidesmosomes are regulated at the post-transcriptional level is poorly understood. Caenorhabditiselegans hemidesmosomes (CeHDs) have a similar structure and composition to their mammalian counterparts, making C. elegans an ideal model for studying hemidesmosomes. Here, we focus on the transcription regulator CCAR-1, identified in a previous genetic screen searching for enhancers of mutations in the conserved hemidesmosome component VAB-10A (known as plectin in mammals). Loss of CCAR-1 function in a vab-10(e698) background results in CeHD disruption and muscle detachment from the epidermis. CCAR-1 regulates CeHD biogenesis, not by controlling the transcription of CeHD-related genes, but by affecting the alternative splicing of unc-52 (known as perlecan or HSPG2 in mammals), the predicted basement extracellular matrix (ECM) ligand of CeHDs. CCAR-1 physically interacts with HRP-2 (hnRNPR in mammals), a splicing factor known to mediate unc-52 alternative splicing to control the proportions of different UNC-52 isoforms and stabilize CeHDs. Our discovery underlines the importance of post-tran...Continue Reading

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Citations

Mar 19, 2020·Journal of Developmental Biology·Cátia A Carvalho, Limor Broday
Nov 21, 2018·Genes·Jerahme R MartinezMary C Farach-Carson
Jul 14, 2018·Aging Cell·Jessica BrunquellSandy D Westerheide

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