GoKawiil
Tech News
Researchers used TBK1-knockout cells and ULK1 knockdown to examine how cells respond to lysosomal stress induced by monensin, nigericin, salinomycin and MG132. Imaging and biochemical analyses showed that loss of TBK1 or ULK1 altered the nuclear-to-cytoplasmic distribution of the transcription factor TFEB, indicating both proteins are needed for its normal activation.
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.
A research team mined all 214.5 million structure predictions in Google DeepMind's AlphaFold database to search for undiscovered 7TM (seven-transmembrane) folds resembling G-protein-coupled receptors. Using the rhodopsin structure as a reference and the TM-align algorithm, they identified TM184C as a previously unrecognized GPCR-like protein involved in regulating cell-to-cell exchange and autophagy. The analysis required processing 24 tebibytes of compressed structural data on university supercomputing clusters.