Related Experiment Video
Updated: May 25, 2026
11:31
Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
Published on: September 18, 2013
Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes
Marita Eckert1,2, Pasquale Miglionico3, Francesca Izzi1
1German Center for Neurodegenerative Diseases, Tübingen, Germany.
EMBO Reports
|May 23, 2026
Summary
Leucine-rich repeat kinase 2 (LRRK2) interactions were mapped using proximity proteomes, revealing its links to cytoskeletal components and cellular compartments. These findings offer new insights into Parkinson's disease mechanisms.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Leucine-rich repeat kinase 2 (LRRK2) is implicated in familial and idiopathic Parkinson's disease (PD).
- LRRK2's multi-domain structure allows complex regulation through intra- and inter-molecular interactions.
Purpose of the Study:
- To identify novel LRRK2 interactors and characterize their functional relationships.
- To elucidate how LRRK2 conformation and activity influence its protein-protein interactions and cellular localization.
Main Methods:
- BioID proximity proteomics to map LRRK2 interactors.
- Evolutionary and structural bioinformatics, including co-evolutionary analysis and AlphaFold-Multimer modeling.
- Analysis of LRRK2 proximity proteome changes induced by MLi-2 inhibitor or RAB29 co-expression.
Main Results:
- Identification of a LRRK2-associated module enriched in cytoskeletal components (centrosome, microtubules).
- Structural modeling revealed distinct interactor groups binding LRRK2 based on specific conformations.
- Changes in LRRK2 interactome were observed upon kinase inhibition or RAB29 expression, linking LRRK2 to centriolar satellites and vesicular compartments.
Conclusions:
- LRRK2 protein-protein interactions are conformation- and activity-dependent.
- These interactions connect LRRK2 to specific cellular sub-compartments, providing mechanistic insights into Parkinson's disease.
- The study provides a comprehensive map of LRRK2 interactions and their regulation.
Related Concept Videos
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...