Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Rab Cascades

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 Rho

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:

Rab Proteins

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...

Cell Polarization by Rho Proteins

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...

RACE - Rapid Amplification of cDNA Ends

RACE - Rapid Amplification of cDNA Ends

Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific primer.
Since the...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Caveolin-1 Phosphorylation Is Essential for Axonal Growth of Human Neurons Derived From iPSCs.

Frontiers in cellular neuroscience·2019

Same author

Engineering Pak1 Allosteric Switches.

ACS synthetic biology·2017

Same author

FRET binding antenna reports spatiotemporal dynamics of GDI-Cdc42 GTPase interactions.

Nature chemical biology·2016

Same author

Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.

Journal of neurovirology·2016

Same author

Correction: Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests.

PLoS genetics·2016

Same author

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer's Disease.

Journal of Alzheimer's disease : JAD·2016

Search research articles

Related Experiment Video

Updated: May 16, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

A novel Rac1 GAP splice variant relays poly-Ub accumulation signals to mediate Rac1 inactivation.

Timothy Y Huang¹, Sarah Michael, Tao Xu

¹Department of Immunobiology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA.

Molecular Biology of the Cell

|December 11, 2012

Summary

A novel brain protein, BARGIN, regulates Rac1 activity by binding to ubiquitin aggregates. This interaction is implicated in neurodegenerative diseases like Alzheimer's, suggesting a new therapeutic target.

More Related Videos

Complementation of Splicing Activity by a Galectin-3 - U1 snRNP Complex on Beads

Complementation of Splicing Activity by a Galectin-3 - U1 snRNP Complex on Beads

Published on: December 9, 2020

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

Related Experiment Videos

Last Updated: May 16, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Complementation of Splicing Activity by a Galectin-3 - U1 snRNP Complex on Beads

Complementation of Splicing Activity by a Galectin-3 - U1 snRNP Complex on Beads

Published on: December 9, 2020

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

Area of Science:

Neurobiology
Molecular Biology
Cellular Signaling

Background:

Spatial regulation of Rho GTPase-activating proteins (GAPs) is poorly understood.
Ubiquitin (Ub) aggregate pathology is central to neurodegenerative disorders.

Purpose of the Study:

To identify and characterize a novel brain-specific RhoGAP splice variant, BARGIN (BGIN).
To investigate the role of BGIN in Rac1 signaling and its potential involvement in neurodegenerative proteotoxicity.

Main Methods:

Described a novel brain-specific RhoGAP splice variant, BARGIN (BGIN).
Utilized biochemical assays to study poly-ubiquitin (poly-Ub)/BGIN interactions.
Analyzed BGIN distribution and Rac1 activity in Alzheimer's disease (AD) brain tissue and an amyloid precursor protein (APP) proteotoxicity model.

Main Results:

BGIN contains BAR, GAP, and poly-Ub-binding CIN domains.
Poly-Ub/BGIN interactions promote BGIN localization to membranes, inactivating membranous Rac1 and downstream reactive oxygen species (ROS) generation.
BGIN/Ub colocalization occurs in AD tangle aggregates, and enhanced BGIN membrane distribution correlates with reduced Rac1 activity in AD brain.
BGIN contributes to Rac1 inhibition and reduced ROS generation in an APP proteotoxicity model.

Conclusions:

BGIN/poly-Ub interactions enhance BGIN membrane localization, relaying poly-Ub signals to inactivate Rac1.
Attenuation of Rac1 signaling is partially BGIN-dependent in a proteotoxic APP context.
BGIN represents a potential link between ubiquitin aggregate pathology and Rac1 signaling in neurodegeneration.