Virally mediated expression of a biologically active peptide to restrain the nuclear functions of ERK1/2 attenuates

Related Experiment Video

Updated: May 22, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

940

Bar Izkovich1, Adonis Yiannakas1,2, Sapir Ne'eman1

  • 1Sagol Department of Neuroscience, University of Haifa, Haifa, Israel.

Molecular Brain
|March 15, 2025
PubMed

Insights

Viral vectors deliver peptides to brain cells, revealing Extracellular signal-regulated kinases 1/2 (ERK1/2) are key for memory extinction, not acquisition or retrieval.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Peptide drug development requires advanced delivery systems to prevent degradation.
  • Extracellular signal-regulated kinases 1/2 (ERK1/2) have critical roles in various cellular compartments.
  • Targeting specific protein functions within distinct cellular locations remains a challenge.

Purpose of the Study:

  • To develop and validate a viral vector-based method for delivering biologically active peptides.
  • To investigate the role of nuclear ERK1/2 in the adult forebrain using this novel delivery system.
  • To specifically attenuate ERK1/2 nuclear functions in targeted brain regions.

Main Methods:

  • Utilized viral vectors for endogenous neurotrophin biogenesis to deliver a therapeutic peptide.
  • Expressed a biologically active peptide to specifically inhibit nuclear ERK1/2 functions.
  • Focused delivery on specific brain areas within the adult forebrain.

Main Results:

  • Demonstrated the feasibility of using viral vectors for targeted peptide delivery and expression.
  • Showed that nuclear ERK1/2 in the forebrain is essential for associative-aversive memory extinction.
  • Found that ERK1/2 nuclear functions are not critical for memory acquisition or retrieval.

Conclusions:

  • Viral vectors offer a viable approach for precise peptide delivery to manipulate cellular processes.
  • Nuclear ERK1/2 plays a specific and crucial role in the extinction of learned fear memories.
  • This technology enables targeted modulation of protein interactions in specific tissues for research and therapeutic potential.

More Related Videos

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment07:55

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

7.8K
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

10.4K

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.2K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.7K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.7K