GoKawiilRNF213 enzyme found to tag defective glycogen for cellular disposal
Researchers identified RNF213, an E3 ubiquitin ligase, as a key surveillance mechanism that marks poorly branched, disease-causing glycogen (polyglucosan) for destruction via autophagy. Mice lacking RNF213's ligase activity built up polyglucosan deposits in the cerebellum, pons, and hippocampus, and cell studies showed the enzyme selectively ubiquitylates abnormal glycogen while a structural domain restrains it from attacking healthy glycogen. Once tagged, the aberrant glycogen recruits autophagy receptors SQSTM1, TAX1BP1, and optineurin, which shuttle it into autophagosomes for clearance.