Cloning and functional characterization of a Na+-independent, broad-specific neutral amino acid transporter from mammalian intestine

D. Prasanna Rajan, Ramesh Kekuda, Wei Huang, Lawrence D Devoe, Frederick H. Leibach, Puttur D Prasad, Vadivel Ganapathy

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We have isolated a cDNA from a rabbit intestinal cDNA library which, when co-expressed with the heavy chain of the human 4F2 antigen (4F2hc) in mammalian cells, induces system L-like amino acid transport activity. This protein, called LAT2, consists of 535 amino acids and is distinct from LAT1 which also interacts with 4F2hc to induce system L-like amino acid transport activity. LAT2 does not interact with rBAT, a protein with a significant structural similarity to 4F2hc. The 4F2hc/LAT2-mediated transport process differs from the 4F2hc/LAT1-mediated transport in substrate specificity, substrate affinity, tissue distribution, interaction with D-amino acids, and pH-dependence. The 4F2hc/LAT2-associated transport process has a broad specificity towards neutral amino acids with K(t) values in the range of 100-1000 μM, does not interact with D-amino acids to any significant extent, and is stimulated by acidic pH. In contrast, the 4F2hc/LAT1-associated transport process has a narrower specificity towards neutral amino acids, but with comparatively higher affinity (K(t) values in the range of 10-20 μM), interacts with some D-amino acids with high affinity, and is not influenced by pH. LAT2 is expressed primarily in the small intestine and kidney, whereas LAT1 exhibits a much broader tissue distribution. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)6-14
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1463
Issue number1
DOIs
StatePublished - Jan 15 2000

Keywords

  • 4F2 heavy chain
  • Amino acid transport
  • Functional expression
  • LAT2
  • Primary structure
  • Rabbit
  • System L

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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