AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans
AP-2-Dependent Endocytic Recycling of the Chitin Synthase Chs3 Regulates Polarized Growth in Candida albicans
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DOI：
10.1128/mbio.02421-18
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Ayscough, K. R.
中科院分区：
文献类型：
--
作者：
Knafler, H. C.;Smaczynska-de Rooij, I. I.;Ayscough, K. R.
已知人类真菌病原体白色念珠菌（Candida albicans）需要内吞作用以使其能够适应不同的小生境并维持其高度极化的菌丝生长阶段。虽然研究已经确定了导致新蛋白质合成和分泌以促进菌丝生长的转录变化，但菌丝的有效维持还需要伴随其他细胞表面分子的去除或重新定位。然而，必须从细胞表面去除的关键分子及其背后的机制仍然难以捉摸。在这项研究中，我们表明，AP-2内吞接头复合物是必需的主要细胞壁生物合成酶Chs 3的内化。我们证明，这种相互作用是由AP-2 μ亚基（Apm 4）YXX Phi结合域介导的。我们还表明，在没有Chs 3通过AP-2回收，细胞有异常的细胞壁组成，有缺陷的极化细胞壁沉积，和形态缺陷。该研究还强调了酵母芽生长的内吞需求与菌丝尖端的内吞需求之间的关键区别，以及AP-2在维持菌丝尖端甘露糖基化蛋白和麦角固醇极性方面的不同需求。总之，我们的研究结果突出了正确的细胞壁沉积的重要性，在细胞形状的维持和极化的增长和内吞循环的关键调节作用，通过AP-2 complex.IMPORTANCE白色念珠菌是一种人类的酵母菌，可以导致显着的发病率和死亡率在免疫功能低下的个人。在人类中，C.白色念珠菌可以采用不同的形态，如酵母或丝状菌丝，并可以占据不同的温度，pH值，CO2水平和营养物质的可用性不同的小生境。形态转换和在不同环境中的生长都需要细胞表面重塑，这涉及添加新合成的蛋白质以及去除其他蛋白质。在我们的研究中，我们证明了适配器复合物AP-2在内化和回收特定的细胞表面酶以维持有效的极化菌丝生长中的重要性。复合物的形成缺陷或其与货物直接相互作用的能力抑制酶的摄取，并导致有缺陷的细胞壁和异常的菌丝形态。我们的数据表明，AP-2适配器在调节念珠菌细胞表面组成中起着核心作用。
The human fungal pathogen Candida albicans is known to require endocytosis to enable its adaptation to diverse niches and to maintain its highly polarized hyphal growth phase. While studies have identified changes in transcription leading to the synthesis and secretion of new proteins to facilitate hyphal growth, effective maintenance of hyphae also requires concomitant removal or relocalization of other cell surface molecules. The key molecules which must be removed from the cell surface, and the mechanisms behind this, have, however, remained elusive. In this study, we show that the AP-2 endocytic adaptor complex is required for the internalization of the major cell wall biosynthesis enzyme Chs3. We demonstrate that this interaction is mediated by the AP-2 mu subunit (Apm4) YXX Phi binding domain. We also show that in the absence of Chs3 recycling via AP-2, cells have abnormal cell wall composition, defective polarized cell wall deposition, and morphological defects. The study also highlights key distinctions between endocytic requirements of growth at yeast buds compared to that at hyphal tips and different requirements of AP-2 in maintaining the polarity of mannosylated proteins and ergosterol at hyphal tips. Together, our findings highlight the importance of correct cell wall deposition in cell shape maintenance and polarized growth and the key regulatory role of endocytic recycling via the AP-2 complex.IMPORTANCE Candida albicans is a human commensal yeast that can cause significant morbidity and mortality in immunocompromised individuals. Within humans, C. albicans can adopt different morphologies as yeast or filamentous hyphae and can occupy different niches with distinct temperatures, pHs, CO2 levels, and nutrient availability. Both morphological switching and growth in different environments require cell surface remodelling, which involves both the addition of newly synthesized proteins as well as the removal of other proteins. In our study, we demonstrate the importance of an adaptor complex AP-2 in internalizing and recycling a specific cell surface enzyme to maintain effective polarized hyphal growth. Defects in formation of the complex or in its ability to interact directly with cargo inhibit enzyme uptake and lead to defective cell walls and aberrant hyphal morphology. Our data indicate that the AP-2 adaptor plays a central role in regulating cell surface composition in Candida.