Topic: SorCS2

The Vps10p-Domain (Vps10p-D) receptor family consists of Sortilin, SorLA, SorCS1, SorCS2 and SorCS3. They mediate internalization and intracellular sorting of specific cargo in various cell types, including neurons, but underlying molecular determinants are incompletely understood. Deciphering the dynamic intracellular itineraries of Vps10p-D receptors is crucial for understanding their role in physiological and cytopathological processes. However, studying their spatial and temporal dynamics by live imaging has been challenging so far, as terminal tagging with fluorophores presumably impedes

SorCS2 is a mammalian sorting receptor that is induced in astrocytes after stroke to support tissue regeneration (Malik et al., Glia 2020). It has been shown that SNP variants of SORCS2 have epistatic effects on Alzheimer’s disease (AD) risk (Reitz et al., Translational Psychiatry 2013), and that SorCS2 deletion in the AD mouse model causes decline in astrocyte number accompanied by a profound increase in toxic amyloid beta (Ab) levels (Network Glia Conference 2023, #341). These observations suggest that astrocyte-expressed SorCS2 may play a protective role not only after stroke, but also in A