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Related Concept Videos

GTPases and their Regulation02:14

GTPases and their Regulation

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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Rab Proteins01:14

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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
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Coat Assembly and GTPases01:33

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Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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Related Experiment Video

Updated: Feb 2, 2026

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

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LRRK2 and Rab GTPases.

Suzanne R Pfeffer1

  • 1Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, U.S.A. pfeffer@stanford.edu.

Biochemical Society Transactions
|November 24, 2018
PubMed
Summary
This summary is machine-generated.

Leucine-rich repeat kinase 2 (LRRK2) mutations activate kinase activity, impacting Parkinson's disease. A screen identified Rab GTPases as LRRK2 substrates, revealing complex roles in membrane trafficking and disease pathology.

Keywords:
LRRK2Parkinson's diseaseRab GTPasekinaseprimary cilia

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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Leucine-rich repeat kinase 2 (LRRK2) mutations are linked to familial Parkinson's disease.
  • Mutant LRRK2 exhibits increased kinase activity.
  • Rab GTPases are key regulators of intracellular membrane trafficking.

Purpose of the Study:

  • To review the relationship between LRRK2 and Rab GTPases.
  • To understand how LRRK2-mediated phosphorylation affects Rab GTPase function.
  • To explore the role of these interactions in Parkinson's disease pathogenesis.

Main Methods:

  • Literature review of studies on LRRK2 and Rab GTPases.
  • Analysis of identified LRRK2 substrates.
  • Discussion of functional consequences of Rab GTPase phosphorylation.

Main Results:

  • A screen identified specific Rab GTPases as direct substrates of LRRK2.
  • Phosphorylation of Rab GTPases by LRRK2 is predicted to alter their function in membrane trafficking.
  • Novel interactions between phosphorylated Rabs and other proteins suggest complex regulatory mechanisms.

Conclusions:

  • LRRK2 directly phosphorylates Rab GTPases, impacting membrane trafficking pathways.
  • These LRRK2-Rab interactions may contribute to the pathology of Parkinson's disease.
  • Further research is needed to fully elucidate the complex roles of LRRK2 in cellular processes and disease.