Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans.
Lag1p and Lac1p catalyse ceramide synthesis in Saccharomyces cerevisiae. This study shows that Lag1 family proteins are generally required for polarized growth in hemiascomycetous yeast. However, in contrast to S. cerevisiae where these proteins are functionally redundant, C. albicans Lag1p (CaLag1p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties, which are involved in generating inositol-containing sphingolipids, whereas CaLac1p produces ceramides with C18:0 fatty acid moieties, which are precursors for glucosylsphingolipids. Thus, our study demonstrates that CaLag1p and CaLac1p have distinct substrate specificities and physiological roles in C. albicans.
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Korea.
Seon Ah
SA
Cheon
Jyotiranjan
J
Bal
Yunkyoung
Y
Song
Hai-Min
HM
Hwang
Ah Ruem
AR
Kim
Woo Kyu
WK
Kang
Hyun Ah
HA
Kang
Hans K
HK
Hannibal-Bach
Jens
J
Knudsen
Christer S
CS
Ejsing
Jeong-Yoon
JY
Kim
D002176:Candida albicans / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D025301:Hyphae / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D002518:Ceramides; D005656:Fungal Proteins; D051049:Sphingosine N-Acyltransferase