Pikachurin Interaction with Dystroglycan is Diminished by Defective O-mannosyl Glycosylation in Congenital Muscular Dystrophy Models and Rescued by LARGE Overexpression

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2010 Dec 7

PMID 21129441

Citations 19

Authors

Huaiyu Hu

Jing Li

Zhen Zhang

Miao Yu

Affiliations

Soon will be listed here.

Abstract

Congenital muscular dystrophies (CMD) such as muscle-eye-brain disease caused by defective glycosylation of α-dystroglycan (α-DG) exhibit defective photoreceptor synaptic function. Mouse knockouts of dystroglycan and its extracellular matrix binding partner pikachurin recapitulate this phenotype. In this study, pikachurin-α-dystroglycan interactions in several mouse models of CMD were examined by pikachurin overlay experiments. The results show that hypoglycosylation of α-dystroglycan resulted in markedly reduced pikachurin-α-dystroglycan interactions. Expression of pikachurin is abolished at the outer plexiform layer of two mouse models, protein O-mannose N-acetylglucosaminyl transferase 1 (POMGnT1) knockout and Large(myd) mice. Overexpressing LARGE restored this interaction in POMGnT1 knockout cells. These results indicate that pikachurin interactions with α-dystroglycan and its localization at the photoreceptor ribbon synapse require normal glycosylation of α-dystroglycan.

Citing Articles

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