Related Experiment Video

Updated: Apr 19, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.7K

Dexamethasone activates transient receptor potential canonical 4 (TRPC4) channels via Rasd1 small GTPase pathway

Jinhong Wie1, Jinsung Kim1,2, Kotdaji Ha1

  • 1Department of Physiology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.

Pflugers Archiv : European Journal of Physiology
|December 16, 2014
PubMed

Insights

The study reveals Rasd1 selectively activates TRPC4 channels, a novel finding. Dexamethasone increases Rasd1, triggering TRPC4 currents, suggesting potential diabetes mellitus therapies.

Area of Science:

  • Molecular Biology
  • Cell Physiology
  • Pharmacology

Background:

  • Canonical transient receptor potential 4 (TRPC4) channels are calcium-permeable cation channels found in mammalian cells.
  • TRPC4 channel activation is typically linked to Gq/11-PLC or Gi/o protein pathways.
  • Previous research focused on heterotrimeric G proteins, leaving the role of small GTPases unexplored.

Purpose of the Study:

  • To investigate the functional relationship between TRPC4 channels and the small GTPase Rasd1.
  • To determine if Rasd1 selectively activates TRPC4 channels and identify necessary co-factors.
  • To explore the effect of dexamethasone on TRPC4 channel activity in pancreatic beta-cells.

Main Methods:

  • Investigated the interaction between Rasd1 and TRPC4 channels using cell-based assays.
  • Examined the role of Gαi1 and Gαi3 proteins in Rasd1-mediated TRPC4 activation.
  • Assessed the impact of dexamethasone on Rasd1 protein expression and TRPC4-like currents in INS-1 cells.

Main Results:

  • Rasd1 was identified as a novel and selective activator of TRPC4 channels among Ras proteins.
  • Functional Gαi1 and Gαi3 proteins were found to be essential for Rasd1-mediated TRPC4 channel activation.
  • Dexamethasone treatment increased Rasd1 protein levels and induced TRPC4-like cationic currents in INS-1 cells.

Conclusions:

  • Rasd1 represents a new class of TRPC4 channel activators.
  • The dexamethasone-Rasd1-TRPC4 pathway offers a potential therapeutic target for managing diabetes mellitus in patients on prolonged dexamethasone therapy.
Keywords:
DexamethasoneGPCRInsulinRasd1Small G proteinTRPC4

More Related Videos

Purification of Endogenous Drosophila Transient Receptor Potential Channels08:39

Purification of Endogenous Drosophila Transient Receptor Potential Channels

Published on: December 28, 2021

2.3K
Controllable Ion Channel Expression through Inducible Transient Transfection10:00

Controllable Ion Channel Expression through Inducible Transient Transfection

Published on: February 17, 2017

10.0K

Related Concept Videos

Small GTPases - Ras and Rho01:24

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:
5.8K
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...
9.5K
GPCRs Regulate Adenylyl Cylase Activity01:09

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...
8.4K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
16.2K
Activation and Inactivation of G Proteins01:22

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...
12.8K
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...
8.9K