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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...

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.

GTPases and their Regulation

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,...

Activation and Inactivation of G Proteins

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

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Related Experiment Video

Updated: Aug 25, 2025

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

Rab GTPases as Modulators of Vascular Function.

Somasundaram Raghavan¹, Masuma Akter Brishti¹, M Dennis Leo¹

¹Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

|October 14, 2022

Summary

Rab GTPases are essential proteins regulating cellular functions like trafficking and exocytosis. This review focuses on their roles in vascular endothelial and smooth muscle cells, highlighting current knowledge gaps.

Keywords:

Rab GTPases endothelial cells vascular smooth muscle

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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

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Published on: November 11, 2018

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Area of Science:

Cell Biology
Molecular Biology
Vascular Biology

Background:

Rab GTPases are a large family of small GTPases crucial for cellular functions, including intracellular trafficking and exocytosis.
Dysregulation of Rab signaling pathways is linked to various diseases.
While Rab GTPase function in endothelial cells is understood, their role in vascular smooth muscle remains less explored.

Purpose of the Study:

To review the current understanding of Rab GTPase functions within the vasculature.
To highlight the known roles in endothelial cells and the limited knowledge in vascular smooth muscle cells.

Main Methods:

Literature review of existing research on Rab GTPases in vascular cells.
Synthesis of available evidence on Rab GTPase involvement in endothelial and smooth muscle cell functions.

Main Results:

Rab GTPases are vital for cellular processes, including vesicle-mediated transport.
Endothelial cells extensively utilize Rab GTPases for functions like regulating vascular tone and inflammatory responses.
Limited studies indicate Rab GTPase involvement in vascular smooth muscle, necessitating further investigation.

Conclusions:

Rab GTPases play critical roles in vascular biology, particularly in endothelial cells.
Further research is required to fully elucidate the functions of Rab GTPases in vascular smooth muscle cells and their implications in vascular diseases.