Endocytosis of nutrient transporters in fungi: the ART of connecting signaling and trafficking

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 include 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.We are grateful to Dr. George Diallinas and Dr. Christos Gournas for their suggestions and critical reading of this manuscript. We thank Dr. Jack Pronk for his fruitful suggestions. Work at CBMA was supported by the ‘‘Contrato-Programa” UIDB/04050/2020 funded by Portuguese national funds through the FCT I.P. BA and RA acknowledge FCT for the PD/BD/135208/2017 and PD/BD/113813/2015 PhD grants, respectively.info:eu-repo/semantics/publishedVersio