Function of the phosphatidylinositol synthase Pis1 in maintenance of endoplasmic reticulum function and pathogenicity

Yingzheng Liu1, Congcong Ma1, Xiaolong Mao1

  • 1Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin 300071, China.

Insights

Phosphatidylinositol synthase (Pis1) is essential for Candida albicans growth. Its overexpression increases fungal virulence and sensitivity to cellular stress, impacting ER stress and cell wall integrity.

Area of Science:

  • Mycology
  • Molecular Biology
  • Biochemistry

Background:

  • Candida albicans is a pathogenic fungus causing widespread infections.
  • Phosphatidylinositols regulate crucial cellular processes like metabolism and growth.
  • The role of phosphatidylinositol synthase (Pis1) in C. albicans was previously uncharacterized.

Purpose of the Study:

  • To identify and characterize the function of Pis1 in Candida albicans.
  • To investigate Pis1's role in cellular stress responses and pathogenicity.

Main Methods:

  • Gene knockout mutant construction using a MET3 promoter-regulated induction system.
  • Green fluorescent protein (GFP) tagging for protein localization.
  • Growth assays, stress sensitivity tests, and virulence assays in mouse models.

Main Results:

  • Pis1 is essential for C. albicans normal growth.
  • Pis1 localizes to the endoplasmic reticulum (ER).
  • Overexpression of PIS1 confers sensitivity to ER and cell wall stress, downregulates stress response genes, enhances extracellular hydrolase secretion, and increases fungal virulence.

Conclusions:

  • Pis1 plays a critical role in Candida albicans physiology.
  • Pis1 is involved in ER stress response and cell wall integrity maintenance.
  • Pis1 positively regulates C. albicans pathogenicity.

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.8K
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...
12.7K
GPI Anchoring of Proteins in the ER Membrane01:29

GPI Anchoring of Proteins in the ER Membrane

GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
4.4K
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...
4.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.5K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.2K