Microdomain Protein Nce102 Is a Local Sensor of Plasma Membrane Sphingolipid Balance.

Area of Science:

• Cell Biology
• Biochemistry
• Microbiology

Background:

• Sphingolipids are crucial for eukaryotic membrane structure and signaling.
• Mechanisms for sensing sphingolipid levels at the plasma membrane are not fully understood.
• Nce102 in Saccharomyces cerevisiae is a candidate sphingolipid sensor.

Purpose of the Study:

• To investigate the role of Nce102 in sensing and regulating sphingolipid levels.
• To determine if Nce102 function is conserved in the human fungal pathogen Candida albicans.
• To explore the physiological significance of Nce102 in response to environmental stress.

Main Methods:

• Microscopy to observe Nce102 plasma membrane distribution.
• Sphingolipid biosynthesis inhibition and precursor supply experiments.
• Mass spectrometry to analyze sphingolipid levels in Nce102 deletion mutants.
• Comparative analysis in Saccharomyces cerevisiae and Candida albicans.

Main Results:

• Nce102 redistributes to sites of high sphingolipid demand, such as nascent bud membranes.
• Nce102 production increases upon sphingolipid biosynthesis inhibition and is internalized when precursors are abundant.
• nce102 deletion mutants exhibit reduced hydroxylated complex sphingolipids under heat stress.
• Nce102 shows analogous responses in Candida albicans, indicating conserved function.

Conclusions:

• Nce102 functions as a sensor for local sphingolipid demand and overall cellular need.
• The Nce102-mediated sphingolipid sensing mechanism is conserved across fungal species.
• This conserved pathway has implications for understanding microbial adaptation and developing new therapeutics.