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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:

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...

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,...

GTPases and their Regulation

GTPases and their Regulation

GPCRs Regulate Adenylyl Cylase Activity

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...

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Related Experiment Video

Updated: Apr 27, 2026

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

Rag GTPases are cardioprotective by regulating lysosomal function.

Young Chul Kim¹, Hyun Woo Park¹, Sebastiano Sciarretta^2,3

¹Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92037, USA.

Nature Communications

|July 2, 2014

Summary

Rag GTPases are crucial for lysosome function and heart health. Loss of RagA/B proteins in heart cells leads to cardiac disease and impaired lysosomal acidification, highlighting their protective role.

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Last Updated: Apr 27, 2026

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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

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The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins

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Published on: December 13, 2013

Area of Science:

Cell Biology
Molecular Biology
Cardiovascular Biology

Background:

Rag GTPases regulate mTORC1 activation by recruiting it to lysosomes.
The in vivo physiological functions of Rag GTPases remain largely unknown.

Purpose of the Study:

To investigate the physiological role of Rag GTPases in vivo.
To explore the impact of RagA/B loss on cardiac function and lysosomal biology.

Main Methods:

Generation of cardiomyocyte-specific RagA/B knockout mice.
Analysis of cardiac morphology and function.
Investigation of lysosomal acidification and v-ATPase levels in knockout cells.

Main Results:

Loss of RagA/B in cardiomyocytes caused hypertrophic cardiomyopathy and lysosomal storage disease phenotypes.
mTORC1 activity was not significantly impaired in vivo despite RagA/B loss.
RagA/B deficiency led to compromised lysosomal acidification and reduced v-ATPase levels, even with TFEB activation.

Conclusions:

RagA/B GTPases are essential regulators of lysosomal function, not solely for mTORC1 activation.
RagA/B proteins play a critical role in maintaining cardiac health and preventing lysosomal dysfunction.
These findings uncover a novel function of Rag GTPases in lysosomal homeostasis and cardiac protection.