Model of clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) in fungal cells. (A) CME in Candida albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe work in a similarly modular way. First, the early module arrives at sites of endocytosis, followed by proteins of the coat, then the Myo/WASP, the actin, and finally the amphyphysin module. After vesicle scission, the cargo-loaded vesicle traffics via endosomes to the vacuole. (B) Currently, two CIE pathways in fungal cells have been described: Rho1-dependent CIE in S. cerevisiae and Arp2/3-independent CIE in C. albicans. Both routes seem not to rely on protein modules of the CME pathway, and yet cargo such as the membrane-impermeable dye FM4-64 still accumulate in the vacuole over time. Rho1-CIE relies on Rho1 and Bni1, while both Rho1-dependent and Arp2/3-independent CIE rely on Arp2/3-independent actin structures. If and how cargo is loaded into vesicles and how cargo crosses the membrane and traffics to the vacuole are unknown both in Rho1-CIE and Arp2/3-independent CIE. Whether Rho1-CIE and Arp2/3-independent endocytosis are one or two distinct ways for CIE remains to be shown. See text for details.