Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression.
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.
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, United States. huh@upstate.edu
Huaiyu
H
Hu
Jing
J
Li
Zhen
Z
Zhang
Miao
M
Yu
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D058494:Walker-Warburg Syndrome / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C553232:pikachurin protein, mouse; D049030:Dystroglycans; C502747:Large1 protein, mouse; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase