SakA MAP kinase is involved in stress signal

© 2002 Blackwell Science LtdSakAMAPkinase is involved in stress signaltransduction, sexual development and spore viabilityin Aspergillus nidulans

differentiation, cell survival and apoptosis in response to diverse extracellular stimuli (reviewed in Herskowitz,1995; Treisman, 1996; Banuett, 1998; Gustin et al., 1998).MAPKs that specifically transmit environmental stresssignals are also known as stress-activated proteinkinases (SAPKs). Members of this MAPK subfamilyinclude Saccharomyces cerevisiaeHog1, Schizosaccha-romyces pombeSpc1 (also called Sty1) and mammalianp38 and JNK MAPKs. Whereas Hog1 is activated mainlyby high osmolarity stress (Brewster et al., 1993; Schulleret al., 1994), mammalian and fission yeast SAPKs areresponsive to various forms of stress, such as hyperos-molarity, heat shock, ultraviolet light irradiation and oxida-tive stress (Millar et al., 1995; Shiozaki and Russell, 1995;Waskiewicz and Cooper, 1995; Degols et al., 1996; Katoet al., 1996; Kyriakis and Avruch, 1996). Indeed, S. cere-visiae hog1mutants are sensitive to high osmolarity,whereas spc1mutations in S. pomberesult in sensitivityto high osmolarity, heat shock and oxidative stress.In multicellular fungi, MAPkinases homologous tobudding yeast Fus3, Kss1 and Slt2 have been identifiedin different species and are implicated in development,hyphal growth and pathogenicity (reviewed in Xu, 2000).On the other hand, the only SAPK homologue that hasbeen studied in some detail is Osm1 in Magnaphorthegrisea(Dixon et al., 1999). The OSM1gene regulates arabitol synthesis in response to hyperosmolarity and itsinactivation results in growth defects and abnormal hyphalmorphology under high osmolarity stress.Our group is interested in understanding how differentenvironmental stress signals can affect developmentaldecisions (Skromne et al., 1995) and stress gene expres-sion (Kawasaki and Aguirre, 2001) in the filamentousascomycete Aspergillus nidulans. This fungus is a well-established model organism for genetic studies of cellu-lar development (Pontecorvo et al., 1953; Martinelli and Kinghorn, 1994; Timberlake and Clutterbuck, 1994;Adams et al., 1998). Depending on the environmentalsignals, A. nidulanscan grow indefinitely or undergo two different, complex developmental programmes.Asexual development (conidiation) is induced by nutrientstarvation stress (Skromne et al., 1995) or by air expo-sure (Clutterbuck, 1972; Law and Timberlake, 1980; Timberlake and Clutterbuck, 1994; Adams et al., 1998).On the other hand, sexual development (formation of

Molecular Microbiology (2002) 45(4), 1153–1163Laura Kawasaki,1Olivia Sánchez,1Kazuhiro Shiozaki2and Jesús Aguirre1,2*1Departamento de Genética Molecular, Instituto de

Fisiología Celular, Universidad Nacional Autónoma deMéxico, Apartado Postal 70–242, 04510 México, D. F.2Section of Microbiology, University of California, Davis,

California 9561, USA.

SummaryIn eukaryotic cells, environmental stress signals aretransmitted by evolutionarily conserved MAPKs, such as Hog1 in the budding yeast Saccharomycescerevisiae, Spc1 in the fission yeast Schizosaccha-romyces pombeand p38/JNK in mammalian cells.Here, we report the identification of the Aspergillusnidulans sakAgene, which encodes a member of thestress MAPK family. The sakAgene is able to com-plement the S. pombe spc1-defects in both osmo-

regulation and cell cycle progression. Moreover,SakAMAPK is activated in response to osmotic andoxidative stress in both S. pombeand A. nidulans.However, in contrast to hog1and spc1mutants, thesakAnull mutant is not sensitive to high osmolaritystress, indicating a different regulation of theosmostress response in this fungus. On the otherhand, the DsakAmutant shows development and cell-specific phenotypes. First, it displays prematuresteA-dependent sexual development. Second, DsakAmutant produces asexual spores that are highly sensitive to oxidative and heat shock stress and loseviability upon storage. Indeed, SakAis transientlyactivated early after induction of conidiation. Ourresults indicate that SakAMAPK is involved in stresssignal transduction and repression of sexual devel-opment, and is required for spore stress resistanceand survival.

IntroductionEukaryotic organisms use different MAPkinase (MAPK)cascades to control gene expression, cell division,

Accepted 23 May, 2002. *For correspondence. E-mail jaguirre@ifisiol.unam.mx; Tel. (+525) 5622 5630; Fax (+525) 5622 5651.