Identifying sacsin interactors. Defining quantitative alterations of the cerebellar proteome in the absence of sacsin.

Sacsin is a huge protein highly expressed in neurons, whose function is still largely unknown. To gain insights into sacsin role in neurons, we performed immunoprecipitation of endogenous sacsin in SH-SY5Y cells differentiated into neurons followed by LC-MS/MS of eluates to identify its interactors. Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in SACS gene encoding sacsin.ARSACS patients and mouse models display early degeneration of cerebellum in agreement with high sacsin expression in this organ. We performed unbiased LFQ proteomics of cerebella from Sacs KO mice versus controls (5 months of age) to dissect the mechanisms underlying cerebellar degeneration in ARSACS.