{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Li X"],"funding":["NINDS NIH HHS"],"pubmed_abstract":["Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes through enhancing the phosphorylation of RAB10 and recruiting Rab interacting lysosomal protein like 1 (RILPL1), while the functions of RAB12 require a direct interaction with LRRK2 an"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.07.17.603999"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11275936"],"repository":["biostudies-literature"],"pubmed_title":["RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes."],"pmcid":["PMC11275936"],"funding_grant_id":["R01 NS129795"],"pubmed_authors":["Li X","Huang BT","Tan H","Xu P","Kim H","Zhang Y","Zhu H","Choi I","Peng J","Sun J","Yue Z"],"additional_accession":[]},"is_claimable":false,"name":"RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes.","description":"Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes through enhancing the phosphorylation of RAB10 and recruiting Rab interacting lysosomal protein like 1 (RILPL1), while the functions of RAB12 require a direct interaction with LRRK2 an","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-04-07T21:19:37.221Z","creation":"2025-04-04T02:58:22.243Z"},"accession":"S-EPMC11275936","cross_references":{"pubmed":["39071328"],"doi":["10.1101/2024.07.17.603999"]}}