Dissection of Transporter Function: From Genetics to Structure

Transporters are transmembrane proteins mediating the selective uptake or efflux of solutes, metabolites, drugs, or ions across cellular membranes. Despite their immense biological importance in cell nutrition, communication, signaling, and homeostasis, their study remains technically difficult mostly due to their lipid-embedded nature. The study of eukaryotic transporters presents additional complexity due to multiple subcellular control mechanisms that operate to ensure proper membrane traffic, membrane localization, and turnover. Model fungi present unique genetic tools to study eukaryotic transporter function. This review highlights how fungal transporter genetics combined with new methodologies for assaying their cellular expression and function as well as recent structural approaches have led to the functional dissection of selected transporter paradigms in Aspergillus nidulans.

TrendsTransmembrane transporters are essential for cellular functioning.Transporter function or malfunction is related to genetic diseases, pathologies, and sensitivity or resistance to drugs.Transporters function by substrate-binding-induced alterations of their protein conformation exposing the substrate-binding site alternatively to either side of the membrane.Genetic analysis of fungal transporters predicted the existence of channel-like gating or filtering domains in transporters before crystal structures were available.Recent crystallographic analyses of transporters reveal mechanistic variations in the outward- to inward-facing alteration of transporters and confirm the presence of gates in transporters.The genetics and crystal structure of the fungal purine transporter UapA show how different gating elements might function and reveal the functional importance of dimerization.