Institut de Génétique et Microbiologie, Université Paris-Sud (XI), UMR 8621 CNRS 91450 Orsay, France.
Mol Microbiol. 2012 May;84(3):530-49. doi: 10.1111/j.1365-2958.2012.08042.x. Epub 2012 Apr 11.
Type I casein kinases are highly conserved among Eukaryotes. Of the two Aspergillus nidulans casein kinases I, CkiA is related to the δ/ε mammalian kinases and to Saccharomyces cerevisiae Hrr25p. CkiA is essential. Three recessive ckiA mutations leading to single residue substitutions, and downregulation using a repressible promoter, result in partial loss-of-function, which leads to a pleiotropic defect in amino acid utilization and resistance to toxic amino acid analogues. These phenotypes correlate with miss-routing of the YAT plasma membrane transporters AgtA (glutamate) and PrnB (proline) to the vacuole under conditions that, in the wild type, result in their delivery to the plasma membrane. Miss-routing to the vacuole and subsequent transporter degradation results in a major deficiency in the uptake of the corresponding amino acids that underlies the inability of the mutant strains to catabolize them. Our findings may have important implications for understanding how CkiA, Hrr25p and other fungal orthologues regulate the directionality of transport at the ER-Golgi interface.
I 型酪蛋白激酶在真核生物中高度保守。在两个 Aspergillus nidulans 酪蛋白激酶 I 中,CkiA 与 δ/ε 哺乳动物激酶和 Saccharomyces cerevisiae Hrr25p 相关。CkiA 是必需的。三个导致单个残基取代的隐性 ckiA 突变,以及使用可诱导的启动子进行下调,导致部分功能丧失,导致氨基酸利用和对有毒氨基酸类似物的抗性的多效缺陷。这些表型与 YAT 质膜转运体 AgtA(谷氨酸)和 PrnB(脯氨酸)在野生型条件下导致其递送至质膜,而在这些条件下错误导向液泡的情况相关。错误导向液泡和随后的转运体降解导致相应氨基酸的摄取严重不足,这是突变株无法分解它们的基础。我们的发现可能对理解 CkiA、Hrr25p 和其他真菌同源物如何调节 ER-Golgi 界面处运输的方向性具有重要意义。