PT - JOURNAL ARTICLE AU - Almeida, Sérgio AU - Miranda, André M. AU - Tóth, Andrea E. AU - Nielsen, Morten S. AU - Oliveira, Tiago Gil TI - SorCS2 deletion leads to altered neuronal lysosome activity AID - 10.1101/2021.04.08.439000 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.08.439000 4099 - http://biorxiv.org/content/early/2021/04/10/2021.04.08.439000.short 4100 - http://biorxiv.org/content/early/2021/04/10/2021.04.08.439000.full AB - Vps10p domain receptors are important for regulating intracellular protein sorting within the central nervous system and as such constitute risk factors for different brain pathologies. Here, we show that removal of SorCS2 leads to altered lysosomal activity in mouse primary neurons. SorCS2-/- neurons show elevated lysosomal markers such as LAMP1 and acidic hydrolases including cathepsin B and D. Despite increased levels, SorCS2-/- neurons fail to degrade cathepsin specific substrates in a live context. SorCS2-deficient mice present an increase in lysolipids, which may contribute to membrane permeabilization and increased susceptibility to lysosomal stress. Our findings highlight SorCS2 as an important factor for a balanced neuronal lysosome milieu.Competing Interest StatementThe authors have declared no competing interest.