D. R. Alessi

Genome-wide screen reveals Rab12 GTPase as a critical activator of pathogenic LRRK2 kinase

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

Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

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.

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

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

Structural basis of human LRRK2 membrane recruitment and activation

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.

A Feed-forward Pathway Drives LRRK2 kinase Membrane Recruitment and Activation

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.

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain

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

Structural basis for the specificity of PPM1H phosphatase for Rab GTPases

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

Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms

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

Accurate MS-based Rab10 phosphorylation stoichiometry determination as readout for LRRK2 activity in Parkinson’s disease

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.

Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

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

Structural basis for Rab8a GTPase recruitment of RILPL2 via LRRK2 phosphorylation of switch 2

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

PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

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.