Background pattern of a brain with neural connections

Team Alessi

Mapping the LRRK2 signalling pathway and its interplay with other Parkinson’s disease components

2020-Present

LRRK2 targets and modifies a set of enzymes known as Rab GTPases, triggering new biological events by creating new protein: protein interactions. We aim to decipher what controls the activity of LRRK2 and to explore, in precise molecular detail, how this enzyme affects three major cellular structures (cilia, lysosomes and mitochondria) implicated in Parkinson’s disease. We showed that mutant LRRK2 triggers a series of molecular changes that cause new sets of proteins to interact. Our goal is to use a combination of state-of-the-art approaches to understand the consequences of these new interactions on the biology of three important subcellular compartments: primary cilia, lysosomes, and mitochondria.

Tags
Ciliogenesis LRRK2 Lysosomes PINK1 Rab

Leadership

Dario Alessi

Dario Alessi

Lead PI (Core Leadership)

Monther Abu-Remaileh

Monther Abu-Remaileh

Co-PI (Core Leadership)

Miratul Muqit

Miratul Muqit

Co-PI (Core Leadership)

Suzanne Pfeffer

Suzanne Pfeffer

Co-PI (Core Leadership)

Enrico Bagnoli

Enrico Bagnoli

Project Manager

Project Highlights

View All

Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved TBM motif

Inherited mutations in VPS35 and the kinase LRRK2 lead to hyperphosphorylation of Rab GTPases and promote the formation of phospho-Rab signalling complexes. A subset of RH2 domain-containing proteins from the RILP-homology family, including RILP, RILPL1, RILPL2, JIP3, and JIP4 are Rab effectors that recognize the LRRK2-phosphorylated switch 2 threonine of...

Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of June 2025. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific category.

Impact

Category

Accolades

Members of the team have been recognized for their contributions.

Open Science Champions

Dario Alessi, Monther Abu-Remaileh, Miratul Muqit, Suzanne Pfeffer, Rotimi Fasimoye, Francesca Tonelli, Toan Phung, Rosamund Shastry, Raja Niujogi, Daniel Saarela

Awards

COSA Prize Winners 2021

2023 Collaborative Meeting

COSA Prize Winners 2024

Network Spotlights

Alexia Kalogeropulou, Francesca Tonelli, Miratul Muqit

In the News

View All

Our Research Teams

Members of the CRN work diligently to advance our understanding of Parkinson’s disease. Learn more about recent CRN discoveries and achievements.

Explore the Research Community