PXD048732-1

PXD048732 is an original dataset announced via ProteomeXchange.

Title	LRRK2-RAB12 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes
Description	Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases and this phosphorylation is elevated by Parkinson’s disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling remains to be elucidated. Here we solve the structure of LRRK2-RAB12 protein complex and reveal a physiological role of RAB12 in the brain. We find that RAB12 corporates with LRRK2 to inhibits the primary ciliogenesis and regulate centrosome homeostasis in astrocytes through recruiting RILPL1 and enhancing the phosphorylation of RAB10, while the functions of RAB12 require a direct interaction with LRRK2 and LRRK2 kinase activity. Furthermore, the ciliary deficits and centrosome alteration caused by the PD-linked LRRK2-G2019S mutation are prevented by disrupting Rab12 in astrocytes. Our study identifies a central role for the LRRK2-RAB12 complex in regulating ciliogenesis and centrosome homeostasis, and the LRRK2-RAB12 structure offers guidance in therapeutic development by targeting the LRRK2-RAB12 interaction.
HostingRepository	PRIDE
AnnounceDate	2025-01-18
AnnouncementXML	Submission_2025-01-17_20:50:13.067.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haiyan Tan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-20 22:30:00	ID requested
⏵ 1	2025-01-17 20:50:13	announced

Li X, Zhu H, Huang BT, Li X, Kim H, Tan H, Zhang Y, Choi I, Peng J, Xu P, Sun J, Yue Z, RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes. Nat Commun, 15(1):8434(2024) [pubmed]

10.1038/s41467-024-52723-6;

submitter keyword: structure of LRRK2-RAB12 protein complex, proteomics,LRRK2, Ciliogenesis, Centrosome Homeostasis, Parkinson’s disease, tandem mass tag

Junmin Peng
contact affiliation	Department of Structural Biology and Developmental Neurobiology, Center for Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
contact email	Junmin.peng@stjude.org
lab head
Haiyan Tan
contact affiliation	St Jude Children's Research Hospital
contact email	haiyan.tan@stjude.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD048732

PRIDE project URI

• PRIDE
  1. PXD048732
     1. Label: PRIDE project
     2. Name: LRRK2-RAB12 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes