Sci. STKE, 31 October 2006
G Protein Signaling Fungal Gib2, an Atypical G Subunit
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
The genome of Cryptococcus neoformans, which causes meningoencephalitis, has been sequenced, revealing three G subunits (Gpa1, Gpa2, and Gpa3) and a single G subunit (Gbp1). Palmer et al. used a yeast two-hybrid screen to identify Gib2 (Gpa1-interacting protein-) as a partner for Gpa1, and this interaction was confirmed by protein pull-down assay. Although sequence comparisons indicated that Gib2 was more similar to proteins of the RACK1 (receptor for activated protein kinase C1) family than to G proteins, modeling of the protein structure revealed a seven-bladed propeller structure like that of G proteins. Yeast two-hybrid assays and pull-down assays confirmed that Gib2 interacted with C. neoformans G proteins (Gpg1 and Gpg2). Overexpression or suppression of Gib2 expression did not alter responsiveness to mating pheromone. However, the Gib2 gene was essential, and analysis of gpa1-deficient strains overexpressing Gib2 showed that Gib2 restored melanin production and capsule formation, two virulence factors. Gib2 also restored cyclic adenosine monophosphate (cAMP) production in gpa1-deficient strains. Thus, Gib2 appears to serve as an atypical G in a cAMP pathway that contributes to virulence in C. neoformans.
D. A. Palmer, J. K. Thompson, L. Li, A. Prat, P. Wang, Gib2, a novel G-like/RACK1 homolog, functions as a G subunit in cAMP signaling and is essential in Cryptococcus neoformans. J. Biol. Chem. 281, 32596-32605 (2006). [Abstract] [Full Text]
Citation: N. R. Gough, Fungal Gib2, an Atypical G Subunit. Sci. STKE 2006, tw370 (2006).
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