Transceptors as a functional link of transporters and receptors

Abstract

Cells need to communicate with their environment in order to obtain nutrients, grow, divide and respond to signals related to adaptation in changing physiological conditions or stress. A very basic question in biology is how cells, especially of those organisms living in rapidly changing habitats, sense their environment. Apparently, this question is of particular importance to all free-living microorganisms. The critical role of receptors, transporters and channels, transmembrane proteins located in the plasma membrane of all types of cells, in signaling environmental changes is well established. A relative newcomer in environment sensing are the so called transceptors, membrane proteins that possess both solute transport and receptor-like signaling activities. Now, the transceptor concept is further enlarged to include micronutrient sensing via the iron and zinc high-affinity transporters of Saccharomyces cerevisiae. Interestingly, what seems to underline the transport and/or sensing function of receptors, transporters and transceptors is ligand-induced conformational alterations recognized by downstream intracellular effectors.

Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells

“…Binding of substrates into the binding pocket used for entry into the translocation channel probably triggers divergent substrate-dependent conformational changes, generating different downstream processes such as transport, signaling, ubiquitination and endocytosis. The results support the concept that different substrates bind to partially overlapping binding sites in the same general substrate-binding pocket of Gap1, triggering divergent conformations, resulting in distinct conformation-induced downstream processes ( Van Zeebroeck et al, 2014 ; Diallinas, 2017 ).…”

Substrate Specificity of the FurE Transporter Is Determined by Cytoplasmic Terminal Domain Interactions

“…In the case of the fungal Mep2 ammonium transporters, which also act as receptors and are thus called transceptors (Diallinas 2017), a CTR has been shown, using both structural and genetic evidence, to act as a domain that dynamically interacts with the main body of the transporter, and is thus directly involved in a mechanism that regulates the opening and closing of the substrate translocation pathway (van den Berg et al 2015). Under nitrogen-sufficient conditions, where Mep2 is not phosphorylated and transport is inactive, the CTR makes relatively few contacts with the main body of the transporter.…”

“…Additionally, given that terminal regions of transporters are little conserved, even among close eukaryotic homologs, it is becoming evident that we cannot predict substrate specificities a priori simply by comparing similarities in substrate-binding sites. Thus, after the recent discovery of dynamic gating elements and oligomerization (Diallinas 2017), terminal cytoplasmic regions, acting as allosteric switches, have come to add an extra level of complexity regarding what determines transporter function and specificity.…”

Forward genetics screen coupled with whole-genome resequencing identifies novel gene targets for improving heterologous enzyme production in Aspergillus niger

“…That mutation of mstC results in increased expression of genes under P glaA could indicate that MstC is involved in nutrient signaling as a transceptor. Initially characterized in Saccharomyces , transceptors have amino acid similarity to—and may function as—transporters, but also act as signal-transducing receptors involved in sensing nutrient availability (Diallinas 2017 ; dos Reis et al 2017 ; Ozcan et al 1996 ). One possible explanation for the impact of ∆ mstC on P glaA -controlled proteins is that mstC encodes (or its deletion induces) a transceptor involved in signaling levels of maltose, glucose, or a combination of the two.…”