D. R. Alessi

The paper identifies Rab12 as a critical activator of pathogenic LRRK2 kinase through a CRISPR-based screen and structural analysis.

This paper introduces Golgi-IP, a method to isolate and analyze the human Golgi's proteome, metabolome, and lipidome, revealing novel components and metabolic features.

This study identifies that PKC isoforms activate LRRK1 by phosphorylating specific residues in the CORB GTPase domain, enhancing kinase activity.

This study determines cryo-EM structures of LRRK2-Rab29 complexes, revealing the structural basis of LRRK2 membrane recruitment and activation, and identifies potential targets for Parkinson's disease treatment.

This study identifies two distinct binding sites on LRRK2 that mediate its membrane recruitment and activation through Rab GTPase interactions, revealing a feed-forward pathway for kinase activity regulation.

The paper shows that LRRK2 mutations and PPM1H loss cause cilia loss in neurons and astrocytes, disrupting Hedgehog signaling in the nigral-striatal pathway.

This paper identifies the structural basis for PPM1H phosphatase specificity for Rab GTPases, showing that a flap domain enables recognition of phosphorylated substrates.

This study identifies distinct Rab proteins phosphorylated by LRRK1 and LRRK2, showing they are regulated by different mechanisms and respond differently to inhibitors.

The paper develops an ultra-sensitive MS-based assay to measure Rab10-Thr73 phosphorylation stoichiometry as a biomarker for LRRK2 activity in Parkinson’s disease.

This study identifies novel SGK3 substrates, including endosomal proteins, through phosphoproteomic screens and shows SGK3 specifically phosphorylates these proteins at sites distinct from Akt.

The paper reports the crystal structure of phospho-Rab8a bound to RILPL2, revealing how LRRK2 phosphorylation enables specific interaction and regulation of ciliogenesis.

This study identifies PPM1H as a phosphatase that counteracts LRRK2 signaling by dephosphorylating Rab proteins, suggesting it as a potential therapeutic target for Parkinson's disease.