Based on all of the substrates for individual, characterized transporters (e

Based on all of the substrates for individual, characterized transporters (e.g. suggest functional synergy between substrate-specific AgNAT6 and AgNAT8 in intracellular absorption of aromatic amino acids. More broadly, they suggest that the specific selectivity, regional expression and polarized membrane docking of NATs represent key adaptive traits shaping functional patterns of essential amino acid absorption in the metazoan alimentary canal Azomycin (2-Nitroimidazole) and other tissues. belongs to a group of tropical culicids that can rapidly develop in freshwater aquatic environments. These adaptations require efficient absorption of nutrients, including 10 essential amino acids (reviewed in Clements, 1992). Accordingly, interruption of an essential amino acid absorption mechanism in mosquito larvae could be employed to reduce the vector component of disease transmission in endemic areas. However, safe and Azomycin (2-Nitroimidazole) effective application of this attractive strategy requires comprehensive understanding of specific and universal properties of essential amino acid transport in target and key risk-of-exposure metazoan organisms. Earlier studies documented the active absorption of essential amino acids in mosquitoes (Uchida et al., 2003; Uchida et al., 2001; Uchida et al., 1990) and other insects (Caccia et al., 2005; Castagna et al., 1997; Giordana et al., 1989; Nedergaard, 1972; Wolfersberger, 2000). Using genome data mining in combination with comparative phylogenetic analysis of transporters in selected organisms with published genomes, we Azomycin (2-Nitroimidazole) identified and compared key families of secondary transporters that contribute to the amino acid traffic network in metazoans (Boudko et al., 2005c). Each identified family provides a unique but complementary part in the contiguous traffic and balance of amino acids; however, the molecular identity and phylogeny of a core mechanism for active absorption of essential amino acids remained uncertain. An intriguing paralogous expansion of orphan transporters was identified among insect members of the sodium neurotransmitter symporter family (SNF; also known as, solute carrier family 6; SLC6) (Boudko et al., 2005a; Boudko et al., 2005b; Boudko et al., 2005c). Based on their phylogenetic closeness with characterized neutral amino acid transporters C two from the tobacco hornworm larva, transporters, several of which are extensively transcribed in the worm alimentary canal (www.wormbase.org). The entire group, designated as nutrient amino acid transporters (NATs), represents a functionally segregated subfamily of SNF ANGPT2 (SLC6) (Boudko et al., 2005a; Boudko et al., 2005b; Boudko et al., 2005c). and have 7, 6 and 9 (possibly +1) NAT members, respectively, demonstrating strong paralogous diversification and variation in gene numbers. This observation suggests that a rapid duplication and functional specialization of NAT members occurs (Boudko et al., 2005a). The retention and consistent expansion of paralogous NATs seen from bacteria to metazoans imply the conservation of a fundamental role of these transporters during metazoan evolution. The NAT-SLC6 population appears to have evolved as an integrated system that performs high-throughput absorption of essential amino acids and their derivatives (Boudko et al., 2005c). Recently, we have cloned and characterized two NATs with unique transport properties from larval midgut (Assis et al., 2004; Boudko et al., 2005b; Meleshkevitch et al., 2006). Both transporters mediate Na+- or K+-coupled voltage-gradient-driven absorption of specific aromatic substrates. However, AgNAT6 (“type”:”entrez-protein”,”attrs”:”text”:”AAT07965″,”term_id”:”46981770″,”term_text”:”AAT07965″AAT07965) preferably absorbs tryptophan and indole-branched substrates, whereas AgNAT8 (“type”:”entrez-protein”,”attrs”:”text”:”AAN40409″,”term_id”:”23955262″,”term_text”:”AAN40409″AAN40409) preferably absorbs phenyl-branched substrates. To determine the physiological significance of such an extraordinary specialization we examined the relative distribution of these aromatic NATs in the model system of the alimentary canal from mosquito larvae. Azomycin (2-Nitroimidazole) In addition, we analyzed the assembly.