Cloning of a lymphatic peptide/histidine transporter

Although peptide transport across the plasma membrane has been characterize d well in the kidney and the intestine, the functional relevance of this tr ansport in other organs has not been addressed. Here we report the cloning of a cDNA for a novel peptide/histidine transporter found in the rat (rPHT2 ), whose mRNA is expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino acids and showed 49% identity with the brain PHT (PHT1 ) [Yamashita, Shimada, Guo, Sate, Kohmura, Hayakawa, Takagi and Tohyama (19 97) J. Biol, Chem. 272, 10205-10211]. rPHT2 mRNA was abundant in lung, sple en and thymus, and detected faintly in brain, liver, adrenal gland and hear t by Northern-blot analysis and reverse transcriptase PCR (RT-PCR). Intense signals for the gene were found in immunocytes using in situ hybridization . Ectopic expression of rPHT2 protein in HEK-293T cells and BHK cells was n or found on the cell surface, but was found on the lysosomal membrane using light- and electron-microscopic analysis, Recombinant rPHT2 protein recons tituted into liposomes showed proton-dependent transport activity with hist idine and histidyl-leucine, These findings suggest that rPHT2 is involved i n the protein catabolic pathway in the lymphatic system.