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Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans.

Publication ,  Journal Article
Nichols, CB; Ost, KS; Grogan, DP; Pianalto, K; Hasan, S; Alspaugh, JA
Published in: Eukaryot Cell
July 2015

The localization and specialized function of Ras-like proteins are largely determined by posttranslational processing events. In a highly regulated process, palmitoyl groups may be added to C-terminal cysteine residues, targeting these proteins to specific membranes. In the human fungal pathogen Cryptococcus neoformans, Ras1 protein palmitoylation is essential for growth at high temperature but is dispensable for sexual differentiation. Ras1 palmitoylation is also required for localization of this protein on the plasma membrane. Together, these results support a model in which specific Ras functions are mediated from different subcellular locations. We therefore hypothesize that proteins that activate Ras1 or mediate Ras1 localization to the plasma membrane will be important for C. neoformans pathogenesis. To further characterize the Ras1 signaling cascade mediating high-temperature growth, we have identified a family of protein S-acyltransferases (PATs), enzymes that mediate palmitoylation, in the C. neoformans genome database. Deletion strains for each candidate gene were generated by homogenous recombination, and each mutant strain was assessed for Ras1-mediated phenotypes, including high-temperature growth, morphogenesis, and sexual development. We found that full Ras1 palmitoylation and function required one particular PAT, Pfa4, and deletion of the PFA4 gene in C. neoformans resulted in altered Ras1 localization to membranes, impaired growth at 37°C, and reduced virulence.

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Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

July 2015

Volume

14

Issue

7

Start / End Page

626 / 635

Location

United States

Related Subject Headings

  • ras Proteins
  • Virulence
  • Signal Transduction
  • Mutation
  • Microbiology
  • Mice, Inbred A
  • Mice
  • Lipoylation
  • Humans
  • Homologous Recombination
 

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Nichols, C. B., Ost, K. S., Grogan, D. P., Pianalto, K., Hasan, S., & Alspaugh, J. A. (2015). Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans. Eukaryot Cell, 14(7), 626–635. https://doi.org/10.1128/EC.00010-15
Nichols, Connie B., Kyla S. Ost, Dayton P. Grogan, Kaila Pianalto, Shirin Hasan, and J Andrew Alspaugh. “Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans.Eukaryot Cell 14, no. 7 (July 2015): 626–35. https://doi.org/10.1128/EC.00010-15.
Nichols CB, Ost KS, Grogan DP, Pianalto K, Hasan S, Alspaugh JA. Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans. Eukaryot Cell. 2015 Jul;14(7):626–35.
Nichols, Connie B., et al. “Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans.Eukaryot Cell, vol. 14, no. 7, July 2015, pp. 626–35. Pubmed, doi:10.1128/EC.00010-15.
Nichols CB, Ost KS, Grogan DP, Pianalto K, Hasan S, Alspaugh JA. Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans. Eukaryot Cell. 2015 Jul;14(7):626–635.

Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

July 2015

Volume

14

Issue

7

Start / End Page

626 / 635

Location

United States

Related Subject Headings

  • ras Proteins
  • Virulence
  • Signal Transduction
  • Mutation
  • Microbiology
  • Mice, Inbred A
  • Mice
  • Lipoylation
  • Humans
  • Homologous Recombination