The MAP kinase signal transduction network in Candida albicans

R Alonso Monge1, E Román1, C Nombela1

  • 1Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain.

Insights

Mitogen-activated protein (MAP) kinase pathways in Candida albicans regulate cell wall integrity, stress responses, and morphology. Understanding these pathways offers potential for new antifungal therapies targeting fungal pathogens.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Mycology

Background:

  • Mitogen-activated protein (MAP) kinase pathways are crucial for cellular responses to environmental stimuli through phosphorylation.
  • In Candida albicans, key MAP kinases include Mkc1, Cek1/2, and Hog1, involved in distinct and overlapping cellular functions.

Purpose of the Study:

  • To elucidate the roles of Mkc1, Cek1/2, and Hog1 MAP kinases in Candida albicans.
  • To explore the broader functions of these pathways beyond their primary roles, including stress response and morphogenesis.
  • To assess the potential of MAPK pathways as targets for novel antifungal therapies.

Main Methods:

  • Genetic analysis of Candida albicans mutants.
  • Phenotypic characterization of MAP kinase mutants.
  • Investigation of stress response and morphogenetic programs.

Main Results:

  • The cell integrity (Mkc1) pathway is vital for cell wall biogenesis.
  • The HOG pathway mediates osmotic stress response, while Cek1 is involved in mating and filamentation.
  • Mkc1 and Hog1 exhibit broader stress-sensing roles; Hog1 also participates in filamentation and chlamydospore formation.
  • Cek1 is implicated in cell wall construction under basal conditions.

Conclusions:

  • MAPK pathways in Candida albicans have diverse and interconnected functions, extending beyond their canonical roles.
  • The involvement of these pathways in responding to host-relevant stimuli explains reduced pathogenicity in certain mutants.
  • MAPK pathways represent a promising target for the development of novel antifungal agents.

Related Concept Videos

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...
Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
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 rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...