Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans
Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans
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DOI：
10.1111/j.1365-2958.2011.07961.x
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发表时间：
2012-02-01
影响因子：
3.6
通讯作者：
Kim, Jeong-Yoon
中科院分区：
文献类型：
--
作者：
Cheon, Seon Ah;Bal, Jyotiranjan;Kim, Jeong-Yoon
Lag 1 p和Lac 1 p催化酿酒酵母中的神经酰胺合成。这项研究表明，Lag 1家族蛋白通常需要在半子囊酵母的极化生长。然而，与S.酿酒酵母中，这些蛋白质是功能冗余的，C.白色念珠菌Lag 1 p（CaLag 1 p）和Lac 1 p（CaLac 1 p）在功能上是不同的。CaLac 1 p的缺失导致了C.白色念珠菌CaLAG 1的缺失降低了菌丝特异性HWP 1和ECE 1基因的表达。此外，过度表达CaLAG 1诱导假菌丝生长在这种生物体在非菌丝诱导条件下，这表明CaLag 1 p是必要的中继信号诱导菌丝特异性基因表达。神经酰胺和鞘脂组成的分析表明，CaLag 1 p主要合成的神经酰胺与C24：0/C26：0脂肪酸部分，这是参与生成肌醇含鞘脂，而CaLac 1 p产生的神经酰胺与C18：0脂肪酸部分，这是葡萄糖鞘脂的前体。因此，我们的研究表明，CaLag 1 p和CaLac 1 p在C.白色念珠菌
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.