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Ras hyperactivation versus overexpression: Lessons from Ras dynamics in Candida albicans
Vavilala A Pratyusha1, Guiliana Soraya Victoria1,2, Mohammad Firoz Khan3,4
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Scientific Reports
|March 29, 2018
Summary
Hyperactivated Ras1 signaling in Candida albicans fungi slows down cell dynamics due to actin polymerization. This hyperactivation, linked to Hsp90 deficiency, can be observed at the single-molecule level using fluorescence correlation spectroscopy.
Area of Science:
- Cell Biology
- Mycology
- Biophysics
Background:
- Ras signaling pathways regulate crucial cellular processes like morphogenesis in eukaryotes.
- Aberrant Ras signaling, termed hyperactivation, can disrupt normal cellular functions.
- Candida albicans, a human pathogen, relies on Ras signaling for its survival and virulence.
Purpose of the Study:
- To investigate the dynamics of hyperactivated Ras1 in Candida albicans.
- To differentiate hyperactivated Ras1 dynamics from normal Ras1 at the single-molecule level.
- To explore the relationship between Ras1 hyperactivation, actin dynamics, and cellular morphology.
Main Methods:
- Utilizing fluorescence correlation spectroscopy (FCS) for near single-molecule level analysis.
- Employing pharmacological agents like jasplakinolide and cytochalasin D to modulate actin polymerization.
- Analyzing Ras1 dynamics in various C. albicans strains, including Hsp90-deficient and sterol-deficient mutants.
Main Results:
- Hyperactivated Ras1 exhibits significantly slower dynamics compared to normal Ras1, attributed to actin polymerization.
- Pharmacological induction of actin polymerization mimics hyperactivated Ras1 dynamics.
- Ras1 hyperactivation, observed in Hsp90-deficient and sterol-deficient mutants, correlates with actin polymerization and co-localizes with G-actin.
- Actin depolymerization accelerates Ras1 dynamics in strains with Ras1 hyperactivation.
Conclusions:
- Ras1 hyperactivation in C. albicans is dynamically distinct from normal Ras1 and is closely linked to actin dynamics.
- The study provides a biophysical method to distinguish between normal and hyperactivated Ras1 signaling.
- Understanding Ras1 hyperactivation and its link to actin polymerization may offer new therapeutic targets against fungal pathogens.
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