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Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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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.
Three regulatory proteins control their activity:
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Rab Proteins01:14

Rab Proteins

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

GTPases and their Regulation

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Rab Cascades01:25

Rab Cascades

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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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The Ras Gene02:38

The Ras Gene

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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...
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Related Experiment Video

Updated: May 1, 2026

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

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The small GTPase Rheb is required for spermatogenesis but not oogenesis.

M D Baker1, M Ezzati, G M Aloisio

  • 1Department of Pathology.

Reproduction (Cambridge, England)
|April 10, 2014
PubMed
Summary

Rheb is essential for male fertility, impacting sperm development and causing sterility in mice lacking it in germ cells. Female mice lacking Rheb show no fertility issues, suggesting compensatory mechanisms in oocytes.

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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates
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Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Cell Signaling

Background:

  • The PI3K-Akt-mTOR pathway is crucial for germ cell development.
  • Sex-specific roles of this pathway's components are increasingly recognized.
  • Rheb's function in germ cells remains largely unexplored.

Purpose of the Study:

  • To investigate the role of Rheb, a key mTORC1 activator, in male and female gametogenesis.
  • To elucidate Rheb's specific functions in spermatogenesis and oogenesis.

Main Methods:

  • Utilized genetic approaches in mice.
  • Generated germ cell-specific Rheb conditional knockout (cKO) models.
  • Conducted detailed phenotypic and fertility analyses.

Main Results:

  • Male germ cell-specific Rheb cKO mice exhibited severe oligoasthenoteratozoospermia and sterility.
  • These males displayed age-dependent meiotic defects and abnormal sperm morphology.
  • Female germ cell-specific Rheb cKO mice were fertile with normal ovarian function and follicle development.

Conclusions:

  • Rheb plays an essential and sex-specific role in spermatogenesis.
  • Rheb deficiency in male germ cells leads to infertility due to developmental defects.
  • Oocytes possess functionally redundant factors that compensate for Rheb loss, unlike male germ cells.