{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Romano LEL"],"funding":["NICHD NIH HHS","Barts Charity","Ataxia UK","NCI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS","Biotechnology and Biological Sciences Research Council"],"pagination":["111580"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9647044"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(5)"],"pubmed_abstract":["Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purk"],"journal":["Cell reports"],"pubmed_title":["Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization."],"pmcid":["PMC9647044"],"funding_grant_id":["A54","P30 CA016086","T32 HD040127","MGU0293","BB/R003335/1","P30 NS045892","U54 HD079124","R01 GM138520"],"pubmed_authors":["Beri J","Chapple JP","Hatimy A","Aw WY","Novoselova TV","Havener TM","Romano LEL","Herring LE","Thalassinos K","Nethisinghe S","Hickey AJ","Wolter JM","Graves LM","Howell S","Xing L","Hixson KM","Perna L","Hall CL","Altadonna GC","Taylor-Blake B"],"additional_accession":[]},"is_claimable":false,"name":"Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization.","description":"Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purk","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-05-31T23:09:34.723Z","creation":"2025-04-04T21:00:32.685Z"},"accession":"S-EPMC9647044","cross_references":{"pubmed":["36323248"],"doi":["10.1016/j.celrep.2022.111580"]}}