Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.
Keywords: AAs, amino acids; ACT, amino Acid/Choline Transporter; AP, adaptor protein; APC, amino acid-polyamine-organocation; Arg, arginine; Arrestins; Arts, arrestin‐related trafficking adaptors; Asp, aspartic acid; Aspergilli; Biotechnology; C, carbon; C-terminus, carboxyl-terminus; Cell factories; Conformational changes; Cu, copper; DUBs, deubiquitinating enzymes; EMCs, eisosome membrane compartments; ER, endoplasmic reticulum; ESCRT, endosomal sorting complex required for transport; Endocytic signals; Endocytosis; Fe, iron; Fungi; GAAC, general amino acid control; Glu, glutamic acid; H+, proton; IF, inward-facing; LAT, L-type Amino acid Transporter; LID, loop Interaction Domain; Lys, lysine; MCCs, membrane compartments containing the arginine permease Can1; MCCs/eisosomes; MCPs, membrane compartments of Pma1; MFS, major facilitator superfamily; MVB, multi vesicular bodies; Met, methionine; Metabolism; Mn, manganese; N, nitrogen; N-terminus, amino-terminus; NAT, nucleobase Ascorbate Transporter; NCS1, nucleobase/Cation Symporter 1; NCS2, nucleobase cation symporter family 2; NH4+, ammonium; Nutrient transporters; OF, outward-facing; PEST, proline (P), glutamic acid (E), serine (S), and threonine (T); PM, plasma membrane; PVE, prevacuolar endosome; Saccharomyces cerevisiae; Signaling pathways; Structure-function; TGN, trans-Golgi network; TMSs, transmembrane segments; TORC1, target of rapamycin complex 1; TRY, titer, rate and yield; Trp, tryptophan; Tyr, tyrosine; Ub, ubiquitin; Ubiquitylation; VPS, vacuolar protein sorting; W/V, weight per volume; YAT, yeast Amino acid Transporter; Zn, Zinc; fAATs, fungal AA transporters.
© 2021 The Authors.