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The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.
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.
Figure 1. The human SLC6 transporters. For hSERT and hGlyT1 the crystal structures are available.
Figure 2. Phylogenetic relationships from selected SLC6 type transporters. Representative members of fish, insect, birds, mammalian -created with Interactive tree of life (https://itol.embl.de/)
Figure 3. Manduca sexta transporters KAAT1 and CAATCH1: Structure, expression, and in vivo operating conditions
Figure 4. Comparison of genomic scaffolds of Manduca sexta and the closely related Bombyx mori and Bombyx mandarina genomes. A Large duplication event seems to be occurred in the Manduca sexta genomic region containing LOC115441498, KAAT1 (LOC11544500), LOC11544502, CAATCH1 (LOC11544501) as evident by comparison to the downstream region containing LOC11544505 and LOC11544504 genes. The region contains scattered along the scaffold other nutrient amino acid transporter genes strongly related to the SLC6 family (see e.g., LOC115441499), which suggest a more complex genomic organization of this area. B Phylogenetic relationships among Lepidopteran (moths and butterflies) sodium-dependent nutrient amino acid transporters (NATs) sharing highest similarities (67–75% identity) with Manduca sexta KAAT1/CAATCH1 transporters
Figure 5. WebLogo of the indicated functional regions. The amino acid sequence considered are indicated and referred to LeuTAa numbering