Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Biophysics | Cell Biology | Fungi | Structural Biology
Ras signaling in response to environmental cues is critical for cellular morphogenesis in eukaryotes. This signaling is tightly regulated and its activation involves multiple players. Sometimes Ras signaling may be hyperactivated. In C. albicans, a human pathogenic fungus, we demonstrate that dynamics of hyperactivated Ras1 (Ras1G13V or Ras1 in Hsp90 deficient strains) can be reliably differentiated from that of normal Ras1 at (near) single molecule level using fluorescence correlation spectroscopy (FCS). Ras1 hyperactivation results in significantly slower dynamics due to actin polymerization. Activating actin polymerization by jasplakinolide can produce hyperactivated Ras1 dynamics. In a sterol-deficient hyperfilamentous GPI mutant of C. albicans too, Ras1 hyperactivation results from Hsp90 downregulation and causes actin polymerization. Hyperactivated Ras1 co-localizes with G-actin at the plasma membrane rather than with F-actin. Depolymerizing actin with cytochalasin D results in faster Ras1 dynamics in these and other strains that show Ras1 hyperactivation. Further, ergosterol does not influence Ras1 dynamics.
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DOI of Published Version
Sci Rep. 2018 Mar 27;8(1):5248. doi: 10.1038/s41598-018-23187-8. Link to article on publisher's site
Pratyusha VA, Victoria GS, Khan MF, Haokip DT, Yadav B, Pal N, Sethi SC, Jain P, Singh SL, Sen S, Komath SS. (2018). Ras hyperactivation versus overexpression: Lessons from Ras dynamics in Candida albicans. Open Access Publications by UMass Chan Authors. https://doi.org/10.1038/s41598-018-23187-8. Retrieved from https://escholarship.umassmed.edu/oapubs/3425
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This work is licensed under a Creative Commons Attribution 4.0 License.