PXD007214

PXD007214 is an original dataset announced via ProteomeXchange.

Title	Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis
Description	We previously reported that Parkinson’s disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on a conserved residue in their switch-II domains (Steger, Tonelli et al., 2016) (PMID: 26824392). Here, we systematically analyzed the Rab protein family and found 14 of them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation for ten of them (Rab3A, Rab3B, Rab3C, Rab3D, Rab8A, Rab8B Rab10, Rab12, Rab35 and Rab43). Affinity enrichment mass spectrometry revealed that the primary ciliogenesis regulators RILPL1 specifically interacts with the LRRK2-phosphorylated forms of Rab8A and Rab10, whereas RILPL2 binds to phosphorylated Rab8A, Rab10, and Rab12. Induction of cilia formation by serum starvation led to a two-fold reduction in ciliogenesis in fibroblasts derived from pathogenic LRRK2-R1441G knock-in mice. These results implicate LRRK2 in primary cilia formation and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies.
HostingRepository	PRIDE
AnnounceDate	2017-11-14
AnnouncementXML	Submission_2017-11-28_00:08:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin Steger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-08 00:08:33	ID requested
1	2017-11-14 08:21:57	announced
⏵ 2	2017-11-28 00:08:05	announced	Updated publication reference for PubMed record(s): 29125462.

Steger M, Diez F, Dhekne HS, Lis P, Nirujogi RS, Karayel O, Tonelli F, Martinez TN, Lorentzen E, Pfeffer SR, Alessi DR, Mann M, Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. Elife, 6():(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: LRRK2, proteomics, RabGTPases, Parkinson's disease

Matthias Mann
contact affiliation	Max Planck Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Martin Steger
contact affiliation	Max Planck Institute of Biochemistry
contact email	steger@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007214
     1. Label: PRIDE project
     2. Name: Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis