The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure\u2013Function Relationships in Mammalian SLC6 Transporters

Michela Castagna,Francesca Vacca,Raffaella Cinquetti,Elena Bossi,Amilcare Barca,Matteo Giovanola,Alessandra Galli,Cristina Roseti,Tiziana Romanazzi,Tiziano Verri

doi:10.1007/s11064-021-03410-1

Michela Castagna, Francesca Vacca + Show 8 more

Open Access

https://doi.org/10.1007/s11064-021-03410-1

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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.

Highlights

Role of Orthologs in Translational ResearchTranslational research applies basic biology to understand the basis of disease and develop new therapies, medical procedures, devices, treatments and other critical medical issues [1]
This review shows how studying KAAT1 and cation–anion-activated amino acid transporter/channel 1 (CAATCH1), two Manduca sexta nutrient transporters both belonging to the Solute carrier 6 (SLC6) family, has led to identifying many novel structural
This review aims to underline the value of insect transporters in the study of the molecular physiology of SLC6 family members

Summary

Introduction

Role of Orthologs in Translational ResearchTranslational research applies basic biology to understand the basis of disease and develop new therapies, medical procedures, devices, treatments and other critical medical issues [1]. Orthologs are genes that evolved by speciation from a common gene that retained a similar function in an ancestral species, while Paralogs are genes that emerged by duplication within a genome and that have often acquired a new function [3,4,5]. Both can be adapted in structure–function studies. The study of the molecular physiology of the SLC6 family members has counted on two special tools of non-human, non-vertebrate origin, i.e., the Lepidopteran amino acid transporters KAAT1 and CAATCH1. This review shows how studying KAAT1 and CAATCH1, two Manduca sexta nutrient transporters both belonging to the SLC6 family, has led to identifying many novel structural

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