Loeb J D, Sepulveda-Becerra M, Hazan I, Liu H
Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697-1700, USA.
Mol Cell Biol. 1999 Jun;19(6):4019-27. doi: 10.1128/MCB.19.6.4019.
Candida albicans undergoes a dramatic morphological transition in response to various growth conditions. This ability to switch from a yeast form to a hyphal form is required for its pathogenicity. The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch. Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida. G1 cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S. cerevisiae. We show that C. albicans CLN1 (CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S. cerevisiae. To investigate whether G1 cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C. albicans, we mutated CaCLN1. Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression. The Cacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media. Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium. Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues.
白色念珠菌会根据各种生长条件发生显著的形态转变。这种从酵母形态转变为菌丝形态的能力是其致病性所必需的。白色念珠菌对传统遗传方法的难处理性阻碍了对控制这种发育转变的分子机制的研究。我们的方法是使用遗传上更易处理的酿酒酵母来获取有关丝状化分子控制的线索,以便在白色念珠菌中进行进一步研究。G1 周期蛋白 Cln1 和 Cln2 已被证明与酿酒酵母的形态发生控制有关。我们发现白色念珠菌的 CLN1(CaCLN1)与酿酒酵母的 CLN1 和 CLN2 具有相同的细胞周期特异性表达模式。为了研究 G1 周期蛋白在白色念珠菌从酵母到菌丝转变过程中是否同样参与细胞形态发生的调控,我们对 CaCLN1 进行了突变。发现 Cacln1/Cacln1 细胞在细胞周期进程中比野生型细胞慢。Cacln1/Cacln1 突变体在几种固体培养基上形成菌丝菌落方面也存在缺陷。此外,虽然突变菌株在几种菌丝诱导条件下能形成芽管,但它们无法在合成菌丝诱导液体培养基中维持菌丝生长模式,并且在这种培养基中菌丝特异性基因的表达存在缺陷。我们的结果表明,CaCln1 可能与信号转导途径协同调节菌丝发育,以响应各种环境线索。