Related Experiment Video

Updated: Jun 17, 2025

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
07:42

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract

Published on: July 1, 2020

5.3K

The ER-Resident Ras Inhibitor 1 (Eri1) of Candida albicans Inhibits Hyphal Morphogenesis via the Ras-Independent

Subhash Chandra Sethi1, Monika Bharati1, Yatin Kumar1

  • 1School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

ACS Infectious Diseases
|August 9, 2024
PubMed

Insights

In Candida albicans, Eri1

Area of Science:

  • Mycology
  • Molecular Biology
  • Biochemistry

Background:

  • Ras signaling and glycosylphosphatidylinositol (GPI) biosynthesis are mutually inhibitory in S. cerevisiae.
  • In contrast, these pathways are mutually activated in C. albicans, controlling virulence.
  • The role of Eri1, a GPI-GnT subunit, in C. albicans was previously unknown.

Purpose of the Study:

  • To investigate the cellular and virulence role of CaEri1 in Candida albicans.
  • To elucidate the interaction of CaEri1 with Ras signaling and GPI biosynthesis pathways.

Main Methods:

  • Genetic manipulation of CaEri1 expression.
  • Analysis of GPI biosynthesis, cell wall integrity, and hyphal morphogenesis.
  • Biochemical assays including pull-down and Förster resonance energy transfer (FRET).
  • Virulence studies in Galleria mellonella.

Main Results:

  • CaEri1 is nonessential for C. albicans viability but its depletion impairs GPI biosynthesis and causes cell wall defects.
  • Severe depletion of CaEri1 leads to hyperfilamentation, suggesting activation of Ras-dependent and independent pathways.
  • CaEri1 interacts with CaRas1 indirectly via CaGpi2 and is downstream of other GPI-GnT subunits in inhibiting Ras-independent filamentation.
  • CaERI1 exhibits unique intersubunit transcriptional cross-talk within the GPI-GnT.
  • A heterozygous CaERI1 strain shows attenuated virulence and enhanced clearance in G. mellonella.

Conclusions:

  • CaEri1 plays a crucial role in regulating GPI biosynthesis, cell wall integrity, and hyphal morphogenesis in C. albicans.
  • CaEri1's interaction network differs from S. cerevisiae, highlighting pathway divergence.
  • CaEri1 is a potential virulence factor and a target for antifungal strategies.
Keywords:
Candida albicans Eri1GPI-N-acetylglucosaminyltransferaseGalleria mellonella infection modelcAMP-PKA signaling, intersubunit regulationhyperfilamentation

More Related Videos

Assay for Adhesion and Agar Invasion in S. cerevisiae04:36

Assay for Adhesion and Agar Invasion in S. cerevisiae

Published on: November 8, 2006

14.9K
Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host09:24

Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host

Published on: October 12, 2022

1.8K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

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...
6.2K
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...
5.3K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
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:
3.9K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K