Mutational Activation of a G_i Causes Uncontrolled Proliferation of Aerial Hyphae and Increased Sensitivity to Heat and Oxidative Stress in Neurospora crassa

Corresponding author: Katherine A. Borkovich, Department of Microbiology and Molecular Genetics, University of Texas, Houston Medical School, 6431 Fannin St., Ste. JFB 1.765, Houston, TX 77030., borkovic{at}utmmg.med.uth.tmc.edu (E-mail)

Communicating editor: R. H. DAVIS

Heterotrimeric G proteins, consisting of , ß, and subunits, transduce environmental signals through coupling to plasma membrane-localized receptors. We previously reported that the filamentous fungus Neurospora crassa possesses a G protein, GNA-1, that is a member of the G_i superfamily. Deletion of gna-1 leads to defects in apical extension, differentiation of asexual spores, sensitivity to hyperosmotic media, and female fertility. In addition, gna-1 strains have lower intracellular cAMP levels under conditions that promote morphological abnormalities. To further define the function of GNA-1 in signal transduction in N. crassa, we examined properties of strains with mutationally activated gna-1 alleles (R178C or Q204L) as the only source of GNA-1 protein. These mutations are predicted to inhibit the GTPase activity of GNA-1 and lead to constitutive signaling. In the sexual cycle, gna-1^R178C and gna-1^Q204L strains are female-fertile, but produce fewer and larger perithecia than wild type. During asexual development, gna-1^R178C and gna-1^Q204L strains elaborate abundant, long aerial hyphae, produce less conidia, and possess lower levels of carotenoid pigments in comparison to wild-type controls. Furthermore, gna-1^R178C and gna-1^Q204L strains are more sensitive to heat shock and exposure to hydrogen peroxide than wild-type strains, while gna-1 mutants are more resistant. In contrast to gna-1 mutants, gna-1^R178C and gna-1^Q204L strains have higher steady-state levels of cAMP than wild type. The results suggest that GNA-1 possesses several Gß-independent functions in N. crassa. We propose that GNA-1 mediates signal transduction pathway(s) that regulate aerial hyphae development and sensitivity to heat and oxidative stresses, possibly through modulation of cAMP levels.

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