POMK regulates dystroglycan function via LARGE1-mediated elongation of matriglycan.

ABSTRACT: Matriglycan [-GlcA-β1,3-Xyl-α1,3-]_n serves as a scaffold in many tissues for extracellular matrix proteins containing laminin-G domains including laminin, agrin, and perlecan. Like-acetyl-glucosaminyltransferase 1 (LARGE1) synthesizes and extends matriglycan on α-dystroglycan (α-DG) during skeletal muscle differentiation and regeneration; however, the mechanisms which regulate matriglycan elongation are unknown. Here, we show that Protein O-Mannose Kinase (POMK), which phosphorylates mannose of core M3 (GalNAc-β1,3-GlcNAc-β1,4-Man) preceding matriglycan synthesis, is required for LARGE1-mediated generation of full-length matriglycan on α-DG (~150 kDa). In the absence of Pomk gene expression in mouse skeletal muscle, LARGE1 synthesizes a very short matriglycan resul

SUBMITTER: Walimbe AS 

PROVIDER: S-EPMC7556876 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature