The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure–Function Relationships in Mammalian SLC6 Transporters

Abstract

To the SLC6 family belong 20 human transporters that utilize the sodium electrochemical gradient to move biogenic amines, osmolytes, amino acids and related compounds into cells. They are classified into two functional groups, the Neurotransmitter transporters (NTT) and Nutrient amino acid transporters (NAT). Here we summarize how since their first cloning in 1998, the insect (Lepidopteran) Orthologs of the SLC6 family transporters have represented very important tools for investigating functional–structural relationships, mechanism of transport, ion and pH dependence and substate interaction of the mammalian (and human) counterparts.

Functional characterization of Atlantic salmon (Salmo salar L.) PepT2 transporters

“…Also, the analysis of the regulation of these transporters remains open for future studies, as well as if and how they differentially respond to various external stimuli and environmental conditions, such as dietary nutrients, salinity and temperature. Finally, the availability of detailed functional data from distant orthologues of the same protein certainly presents a key tool for investigating how single determinants could be responsible for subtle functional differences (Castagna et al., 2022), as the differences in sequence can easily be related to differences in the kinetic or biophysical parameters. From this point of view, the data here reported will surely help in the investigation on the structure–function relationships within the peptide transporter family.…”

Functional characterization of Atlantic salmon (Salmo salar L.) PepT2 transporters

“…Also, the analysis of the regulation of these transporters remains open for future studies, as well as if and how they differentially respond to various external stimuli/environmental conditions, such as dietary nutrients, salinity, and temperature. Finally, the availability of detailed functional data from distant orthologs of the same protein certainly represents a key tool for investigating how single determinants can be responsible for subtle functional differences (Castagna et al ., 2022), as the differences in sequence can easily be related to differences in the kinetic or biophysical parameters. From this point of view, the data here reported will surely be of help in the deep investigation on the structure-function relationships within the peptide transporters family.…”

The “www” of Xenopus laevis Oocytes: The Why, When, What of Xenopus laevis Oocytes in Membrane Transporters Research

“…The possibility of changing specific residues can also modify the electrogenicity of the transporter [ 66 ] or explain the differences between orthologs; this approach is widely used to recognize the activity of mammalian transporters [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”