Dtr1p, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae

Dtr1p, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae
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DOI:
10.1128/ec.1.5.799-810.2002
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发表时间:
2002-10-01
期刊:
影响因子:
--
通讯作者:
Briza, P
Briza, P
中科院分区:
其他
文献类型:
--
作者:
Felder, T;Bogengruber, E;Briza, P

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二倍体母细胞内多层孢子壁的重新形成是酿酒酵母产孢的一个重要标志。富含二酪氨酸的外孢子壁的合成发生在这个过程的最后。双甲酰基二酪氨酸是孢子表面的主要组成部分,它在原孢子的细胞质中经过多步骤合成,并被运送到成熟的细胞壁中。在孢子表面聚合成高度交联的大分子。本研究表明,孢子形成特异性蛋白Dtr1p(由YBR180w编码)通过促进二甲酰二酪氨酸通过孢子膜转运,在孢子壁合成中发挥重要作用。DTR1在孢子壁突变体的全基因组筛选中被鉴定出来。零突变体在细胞质中积累了异常大量的二甲酰二酪氨酸,不能有效地将这种前体结合到孢子表面。因此,许多突变孢子具有异常的表面结构。Dtr1p是DHA12(具有12个预测膜跨度的药物:H+反转运蛋白)家族的一员,在孢子成熟过程中定位于前体膜。Dtr1p的转运可能不局限于其天然底物二甲酰基二酪氨酸。当在营养细胞中表达时,Dtr1p使这些细胞对不相关的有毒化合物(如抗疟疾药物和食品级有机酸防腐剂)的抵抗力略强。Dtr1p是在酵母细胞中具有指定生理作用的主要促进物超家族的第一个多药耐药蛋白。
The de novo formation of multilayered spore walls inside a diploid mother cell is a major landmark of sporulation in the yeast Saccharomyces cerevisiae. Synthesis of the dityrosine-rich outer spore wall takes place toward the end of this process. Bisformyl dityrosine, the major building block of the spore surface, is synthesized in a multistep process in the cytoplasm of the prospores, transported to the maturing wall, and. polymerized into a highly cross-linked macromolecule on the spore surface. Here we present evidence that the sporulation-specific protein Dtr1p (encoded by YBR180w) plays an important role in spore wall synthesis by facilitating the translocation of bisformyl dityrosine through the prospore membrane. DTR1 was identified in a genome-wide screen for spore wall mutants. The null mutant accumulates unusually large amounts of bisformyl dityrosine in the cytoplasm and fails to efficiently incorporate this precursor into the spore surface. As a result, many mutant spores have aberrant surface structures. Dtr1p, a member of the poorly characterized DHA12 (drug:H+ antiporter with 12 predicted membrane spans) family, is localized in the prospore membrane throughout spore maturation. Transport by Dtr1p may not be restricted to its natural substrate, bisformyl dityrosine. When expressed in vegetative cells, Dtr1p renders these cells slightly more resistant against unrelated toxic compounds, such as antimalarial drugs and food-grade organic acid preservatives. Dtr1p is the first multidrug resistance protein of the major facilitator superfamily with an assigned physiological role in the yeast cell.