The AP-2 endocytic adaptor complex in Candida albicans morphology and virulence

Fungi such as Candida species are a major cause of hospital-acquired infections especially in immuno-compromised patients, and invasive candidiasis is associated with a high mortality rate. Central to Candida albicans virulence is its ability to switch between budding (yeast) and filamentous (hyphal) growth, and to colonise different body niches. In each distinct environment it must remodel its cell surface to ensure appropriate levels of transporters and cell wall biosynthesis enzymes. Endocytosis is known to be a critical pathway in surface remodelling, allowing cells to internalise proteins that are no longer needed at the plasma membrane. Endocytosis is also crucial to highly polarised hyphal growth, where endocytic recycling of key membrane proteins is essential to maintain their polarised location at the hyphal tip. The aim of this study is to investigate the role of the AP-2 endocytic adaptor complex in endocytosis within C. albicans. Homozygous deletions were generated in an essential subunit of the AP-2 complex. The deletion did not affect rates of cell growth or fluid phase endocytosis, but using fluorescence and electron microscopy, defects were observed in hyphal polarisation and in cell wall organisation. We have shown that the AP-2 complex is required for the recycling of the key cell wall biosynthesis enzyme Chs3, via its Yxxφ internalisation motif(s). We demonstrate this interaction is critical for correct cell wall deposition and polarised growth. Thus, AP-2 mediated endocytic recycling is a key step in the regulation of the fungal cell wall.