Ekena Joanne L, Stanton Brynne C, Schiebe-Owens Jessica A, Hull Christina M
University of Wisconsin, Madison, 587 Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA.
Eukaryot Cell. 2008 Jan;7(1):49-57. doi: 10.1128/EC.00377-07. Epub 2007 Nov 9.
Sexual development in the human fungal pathogen Cryptococcus neoformans is a multistep process that results in the formation of spores, the likely infectious particles. A critical step in this developmental process is the transition from bud-form growth to filamentous growth. This transition is controlled by the homeodomain transcription factors Sxi1alpha and Sxi2a, whose targets are largely unknown. Here we describe the discovery of a gene, CLP1, that is regulated by Sxi1alpha and Sxi2a and is essential for sexual development. In vitro binding studies also show that the CLP1 promoter is bound directly by Sxi1alpha and Sxi2a. The deletion of CLP1 leads to a block in sexual development after cell fusion but before filament formation, and cells without CLP1 are unable to grow vegetatively after cell fusion. Our findings lead to a model in which CLP1 is a downstream target of the Sxi proteins that functions to promote growth after mating and to establish the filamentous state, a critical step in the production of spores.
人类真菌病原体新型隐球菌的性发育是一个多步骤过程，最终会形成孢子，而孢子可能是感染性颗粒。这一发育过程中的关键步骤是从芽状生长向丝状生长的转变。这一转变由同源结构域转录因子Sxi1alpha和Sxi2a控制，但其靶标大多未知。在此，我们描述了一个受Sxi1alpha和Sxi2a调控且对性发育至关重要的基因CLP1的发现。体外结合研究还表明，CLP1启动子直接与Sxi1alpha和Sxi2a结合。CLP1的缺失导致细胞融合后但在丝状形成之前的性发育受阻，且没有CLP1的细胞在细胞融合后无法进行营养生长。我们的研究结果得出一个模型，其中CLP1是Sxi蛋白的下游靶标，其作用是促进交配后的生长并建立丝状状态，这是孢子产生过程中的关键步骤。
