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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.
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Related Experiment Video

Updated: May 26, 2025

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
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Different Ras isoforms regulate synaptic plasticity in opposite directions.

Esperanza López-Merino1, Alba Fernández-Rodrigo1,2, Jessie G Jiang1

  • 1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.

The EMBO Journal
|February 21, 2025
PubMed
Summary
This summary is machine-generated.

The small GTPase Ras signaling pathway is crucial for memory. Researchers found H-Ras mediates long-term depression, while K-Ras supports long-term potentiation, impacting cognitive function.

Keywords:
HippocampusMemoryRASopathiesSpinemGluR

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The Ras GTPase is a key intracellular signaling hub vital for hippocampal long-term potentiation (LTP) and memory formation.
  • RASopathies, resulting from genetic alterations in Ras signaling, are associated with human cognitive disorders.
  • The specific roles of different Ras isoforms in neuronal function and synaptic plasticity remain largely undefined.

Purpose of the Study:

  • To elucidate the distinct functions of H-Ras and K-Ras isoforms in synaptic plasticity and memory.
  • To investigate the molecular mechanisms by which H-Ras regulates synaptic function and cognitive processes.

Main Methods:

  • Utilized genetically modified mice to study H-Ras and K-Ras function in vivo.
  • Investigated synaptic plasticity, including long-term potentiation (LTP) and metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD).
  • Analyzed molecular signaling pathways, including c-Src, Erk activation, and de novo protein synthesis, in response to H-Ras activation.

Main Results:

  • H-Ras, the most abundant brain isoform, was found to mediate mGluR-LTD, not LTP.
  • H-Ras activation in spines during mGluR-LTD requires c-Src and triggers Erk activation and protein synthesis.
  • Deletion of H-Ras impaired object recognition, social, and spatial memory.
  • K-Ras was identified as the isoform specifically required for LTP.
  • Differential synaptic localization of H-Ras and K-Ras was observed.

Conclusions:

  • H-Ras and K-Ras exhibit functional specialization in regulating synaptic plasticity, with H-Ras mediating LTD and K-Ras mediating LTP.
  • These findings highlight the distinct roles of Ras isoforms in neuronal function and have implications for understanding cognitive disorders associated with RASopathies.