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.
Rights and Permissions
Copyright © The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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 Articles. https://doi.org/10.1038/s41598-018-23187-8. Retrieved from https://escholarship.umassmed.edu/oapubs/3425
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.