Sacsin, the ARSACS disease protein, controls lysosomal positioning and reformation by regulating microtubule dynamics

ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a fatal brain disorder featuring cerebellar neurodegeneration leading to spasticity and ataxia. ARSACS is caused by mutations in the SACS gene that encodes sacsin, a massive 4579 amino acid protein with multiple modular domains. Here we demonstrate that sacsin binds to microtubules and regulates microtubule dynamics. Loss of sacsin function in knockout cell lines, knockdown and knockout neurons, and patient fibroblasts leads to alterations in lysosomal transport, positioning, function and reformation following autophagy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast

SUBMITTER: Vincent Francis  

LAB HEAD: Peter McPherson

PROVIDER: PXD033823 | Pride | 2022-10-15

REPOSITORIES: Pride