We recently discovered that chains of the LRRK2 protein can wrap around cellular highways called “microtubules”. Our work suggests that LRRK2 blocks the cellular machines that move on these highways. We will explore the idea that mutations in LRRK2 cause PD by acting as roadblocks that change the normal transport of chemical information inside cells. We will test additional ideas that arise from the experiments we perform. Our collaborative team includes experts in cryo-electron microscopy (Cryo-EM), cryo-electron tomography (Cryo-ET), small molecule synthesis, proteomics, and single-molecule and live-cell imaging. We will use our expertise to solve structures of multiple conformations and variants of LRRK2 to manipulate these different pools of LRRK2 and understand their cellular functions. We will determine how LRRK2 binds to microtubules and affects microtubule-based motors. We will also identify the protein interaction landscape of LRRK2 and test emergent cellular hypotheses resulting from this work, including whether LRRK2 regulates the transport of chemical information on microtubules.
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
Members of the team have been recognized for their contributions.
Awards
Updates will be posted when available.
Members of the CRN work diligently to advance our understanding of Parkinson’s disease. Learn more about recent CRN discoveries and achievements.
