Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Aberdeen Fungal Group, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, United Kingdom.
mBio. 2019 Mar 19;10(2):e02421-18. doi: 10.1128/mBio.02421-18.
The human fungal pathogen 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) YXXΦ 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. is a human commensal yeast that can cause significant morbidity and mortality in immunocompromised individuals. Within humans, can adopt different morphologies as yeast or filamentous hyphae and can occupy different niches with distinct temperatures, pHs, CO 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 .
人源真菌病原体 需要内吞作用来适应不同的生态位并维持其高度极化的菌丝生长阶段。虽然研究已经确定了转录变化，导致新蛋白质的合成和分泌，以促进菌丝生长，但有效地维持菌丝还需要同时去除或重新定位其他细胞表面分子。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 内吞衔接复合物对于主要细胞壁生物合成酶 Chs3 的内化是必需的。我们证明这种相互作用是由 AP-2 μ亚基（Apm4）YXXΦ 结合域介导的。我们还表明，在没有 Chs3 通过 AP-2 回收的情况下，细胞的细胞壁组成异常，极化细胞壁沉积缺陷，形态缺陷。该研究还强调了在酵母芽与菌丝尖端相比以及在维持菌丝尖端甘露糖化蛋白和麦角固醇极性方面 AP-2 的不同要求之间，内吞作用对生长的需求之间的关键区别。总之，我们的研究结果强调了正确的细胞壁沉积在细胞形状维持和极化生长中的重要性，以及通过 AP-2 复合物进行内吞作用回收的关键调节作用。 是一种人共生酵母，可在免疫功能低下的个体中引起严重的发病率和死亡率。在人体内， 可以采用酵母或丝状菌丝的不同形态，并可以占据具有不同温度、pH 值、CO 水平和营养可用性的不同生态位。形态转换和在不同环境中生长都需要细胞表面重塑，这涉及新合成蛋白质的添加以及其他蛋白质的去除。在我们的研究中，我们证明了衔接复合物 AP-2 在内化和回收特定细胞表面酶以维持有效极化菌丝生长中的重要性。该复合物的形成缺陷或其与货物直接相互作用的能力缺陷会抑制酶摄取，导致细胞壁缺陷和菌丝形态异常。我们的数据表明，AP-2 衔接物在 中调节细胞表面组成方面起着核心作用。
