Related Experiment Video

Updated: Feb 13, 2026

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

16.1K

The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2

Panagiotis S Athanasopoulos1,2, Rolf Heumann2, Arjan Kortholt1

  • 1Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, The Netherlands.

Biological Chemistry
|March 15, 2018
PubMed

Insights

Mutations in leucine-rich-repeat kinase 2 (LRRK2) cause Parkinson's Disease. This study explores how LRRK2 phosphorylation sites regulate its function and role in PD pathogenesis.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Mutations in human leucine-rich-repeat kinase 2 (LRRK2) are the most frequent cause of late-onset Parkinson's Disease (PD).
  • LRRK2 possesses GTPase and kinase domains, and its function is modulated by phosphorylation.
  • Specific phosphorylation sites are critical for LRRK2 localization and PD pathogenesis.

Purpose of the Study:

  • To discuss the role of LRRK2 (auto)-phosphorylation sites in Parkinson's Disease.
  • To elucidate the regulation of these phosphorylation sites by phosphatases and upstream kinases.

Main Methods:

  • Literature review and discussion of existing research on LRRK2 phosphorylation.
  • Analysis of the impact of phosphorylation on LRRK2 GTPase activity and localization.

Main Results:

  • A cluster of N-terminal (auto)-phosphorylation sites is crucial for LRRK2 localization and PD pathogenesis.
  • Phosphorylation within the G-domain affects LRRK2 GTPase activity.
  • Phosphatases and upstream kinases play a regulatory role in LRRK2 phosphorylation.

Conclusions:

  • Understanding LRRK2 phosphorylation is key to understanding Parkinson's Disease.
  • Regulation of LRRK2 phosphorylation by kinases and phosphatases is a critical aspect of PD pathogenesis.
Keywords:
GTPaseParkinson’s diseasekinaseneuronal degenerationphosphatases

More Related Videos

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation12:49

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Published on: March 21, 2020

8.0K
Assaying the Kinase Activity of LRRK2 in vitro06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

23.0K

Related Concept Videos

Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
54.4K
Reaction Mechanisms03:06

Reaction Mechanisms

Chemical reactions often occur in a stepwise fashion, involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs.
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
31.2K
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.9K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Role of Septins01:02

Role of Septins

Septins are the recently discovered fourth major protein component of the cytoskeleton, along with microfilaments, microtubules, and intermediate filaments. These proteins can associate with other cytoskeletal filaments and carry out varied roles or can be free-floating in the cytoplasm.
Cellular Functions of Septins
Recent studies have revealed the multifaceted roles of septins in various cellular processes such as cytokinesis, ciliogenesis, and neurogenesis. Septins act as scaffolds and...
2.2K
Complex Numbers01:29

Complex Numbers

The real number system cannot represent the square root of a negative number, which restricts solutions for certain equations, such as quadratics with negative discriminants. To address this, the complex number system was developed, introducing the imaginary unit i, where i = √(-1). This extension allows for the representation of all roots, including those involving negative radicands.A complex number is written in the form x + yi, where x and y are real numbers. Here, x represents the...
324