Affiliation:
1. Rosalind Franklin University of Medicine & Science
Abstract
Summary
Nutrient Amino acid Transporters (NATs) of SoLute Carrier family 6 (SLC6) mediate uptake of essential amino acids in mammals and insects. Phylogenomic analysis of the Caenorhabditis elegans (Ce) SLC6 family identifies 5 genes paralogous to an insect-specific NAT subfamily. Here we cloned and characterized the first representative of the identified nematode-specific transporters, SNF-5. SNF-5 mediates broad spectrum cation-coupled transport of neutral amino acids with submillimolar affinities and stoichiometry of 1AA:1Na+, except for 1L-Pro:2 Na+. Unexpectedly, it transports acidic L-Glu- and L-Asp- (AA -1:3Na+), revealing it to be the first member of a new B0,- system among characterized SLC6 transporters. This activity correlates with a unique positively charged His+ 377 in the substrate-binding pocket. snf-5 promoter-driven EGFP labels intestinal cells INT1-9 and three pairs of amphid sensory neurons: ASI, ADF, and ASK. These cells are intimately involved in control of dauer diapause, development, metabolism, and longevity. The snf-5 deletion mutants do not show apparent morphological disorders, but increase dauer formation while reducing dauer maintenance upon starvation. Overall, our studies characterized the first nematode-specific NAT and revealed important structural and functional aspects of this transporter. In addition to the predictable role in alimentary amino acid absorption, our results indicate possible neuronal roles of SNF-5 as an amino acid provider to specific neuronal functions, including sensing of amino acid availability.
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
Cited by
9 articles.
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