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Related Concept Videos

Rab Proteins01:14

Rab Proteins

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.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab Cascades01:25

Rab Cascades

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.
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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.
Three regulatory proteins control their activity:
GTPases and their Regulation02:14

GTPases and their Regulation

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.
Large G-proteins, also known...
GTPases and their Regulation02:14

GTPases and their Regulation

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.
Large G-proteins, also known...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...

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Related Experiment Video

Updated: May 19, 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

Elucidating the molecular interplay between LRRK2 and Rab GTPases.

Hanwen Zhu1,2, Liam Eade3,2, Dario R Alessi3

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Biorxiv : the Preprint Server for Biology
|May 18, 2026
PubMed
Summary
This summary is machine-generated.

Gain-of-function mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) drive Parkinson's disease. This study reveals novel binding sites on LRRK2 for Rab GTPases, crucial for understanding disease mechanisms and developing therapies.

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Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
12:49

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

Published on: March 21, 2020

Related Experiment Videos

Last Updated: May 19, 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

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
12:49

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

Published on: March 21, 2020

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Gain-of-function mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are a primary genetic cause of inherited Parkinson's disease.
  • LRRK2 is a kinase that interacts with Rab GTPases, regulating cellular functions including lysosomal homeostasis.
  • The molecular mechanisms dictating selective Rab recognition by LRRK2 are not fully understood.

Purpose of the Study:

  • To structurally characterize LRRK2 interactions with Rab GTPases.
  • To identify novel LRRK2-binding sites on Rabs.
  • To provide a structural basis for understanding LRRK2 regulation and targeting it therapeutically.

Main Methods:

  • Structural characterization of LRRK2-Rab GTPase complexes.
  • Identification and mapping of Rab-binding sites on LRRK2.
  • Analysis of LRRK2 interactions with GABARAP.

Main Results:

  • Three new Rab-binding sites (site 4 for Rab8A/10, site 5 for Rab43, site 6 for Rab5A) were identified on LRRK2.
  • A total of six distinct LRRK2-binding sites were defined, accounting for known Rab interactions.
  • The binding site for GABARAP, which recruits LRRK2 to stressed lysosomes, was elucidated.

Conclusions:

  • The identified LRRK2-binding sites provide a structural framework for understanding Rab recognition.
  • These findings offer insights into LRRK2 regulation by Rabs and GABARAP.
  • The study lays the groundwork for therapeutic strategies targeting LRRK2 recruitment in Parkinson's disease.