LRRK2

Cilia effects upon perturbation of LRRK2

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Decreased cilia number

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

basal body, cytosol, microtubules

References: PMID:41005307, PMID:30398148, PMID:29125462, PMID:39343966, PMID:39088390, PMID:34230223

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Protein processing & maturation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Cilia length regulation

Function

Phosphorylates Rab8A, Rab10 and Rab12, mutations interferer with primary cilia formation by generating pRab10 that binds endogenous RILPL1 and blocks cilia formation. Regulates intracellular vesicular traffic during ciliogenesis (30398148, 29125462). RAB12-LRRK2 complex suppresses primary ciliogenesis … the ciliated cell percentage, cilia length, and cilia volume were quantified in astrocytes …(39343966) Activating LRRK2 mutations cause Parkinson’s and block primary cilia formation in specific cells in the mouse brain. (39088390) Some data suggest LRRK2 kinase activity may not directly regulate ciliogenesis depending on cell type. (30398148) (34230223)