HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 29, 27221-27230, July 20, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/29/27221    most recent M100737200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tailor, C. S. Articles by Kabat, D. Search for Related Content PubMed PubMed Citation Articles by Tailor, C. S. Articles by Kabat, D. Social Bookmarking                      What's this?

Truncated Forms of the Dual Function Human ASCT2 Neutral Amino Acid Transporter/Retroviral Receptor Are Translationally Initiated at Multiple Alternative CUG and GUG Codons^*

Chetankumar S. Tailor^§, Mariana Marin, Ali Nouri, Michael P. Kavanaugh^¶, and David Kabat^*

From the  Department of Biochemistry and Molecular Biology and the ^¶ Vollum Institute, Oregon Health Sciences University, Portland, Oregon 87201-3098

The sodium-dependent neutral amino acid transporter type 2 (ASCT2) was recently identified as a cell surface receptor for endogenously inherited retroviruses of cats, baboons, and humans as well as for horizontally transmitted type-D simian retroviruses. By functional cloning, we obtained 10 full-length 2.9-kilobase pair (kbp) cDNAs and two smaller identical 2.1-kbp cDNAs that conferred susceptibility to these viruses. Compared with the 2.9-kbp cDNA, the 2.1-kbp cDNA contains exonic deletions in its 3' noncoding region and a 627-bp 5' truncation that eliminates sequences encoding the amino-terminal portion of the full-length ASCT2 protein. Although expression of the truncated mRNA caused enhanced amino acid transport and viral receptor activities, the AUG codon nearest to its 5' end is flanked by nucleotides that are incompatible with translational initiation and the next in-frame AUG codon is far downstream toward the end of the protein coding sequence. Interestingly, the 5' region of the truncated ASCT2 mRNA contains a closely linked series of CUG(Leu) and GUG(Val) codons in optimal consensus contexts for translational initiation. By deletion and site-directed mutagenesis, cell-free translation, and analyses of epitope-tagged ASCT2 proteins synthesized intracellularly, we determined that the truncated mRNA encodes multiple ASCT2 isoforms with distinct amino termini that are translationally initiated by a leaky scanning mechanism at these CUG and GUG codons. Although the full-length ASCT2 mRNA contains a 5'-situated AUG initiation codon, a significant degree of leaky scanning also occurred in its translation. ASCT2 isoforms with relatively short truncations were active in both amino acid transport and viral reception, whereas an isoform with a 79-amino acid truncation that lacked the first transmembrane sequence was active only in viral reception. We conclude that ASCT2 isoforms with truncated amino termini are synthesized in mammalian cells by a leaky scanning mechanism that employs multiple alternative CUG and GUG initiation codons.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF334818.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. J. Pinho, V. Pinto, M. P. Serrao, P. A. Jose, and P. Soares-da-Silva Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R538 - R547. [Abstract] [Full Text] [PDF]

				J. K. Brown, C. Fung, and C. S. Tailor Comprehensive Mapping of Receptor-Functioning Domains in Feline Leukemia Virus Subgroup C Receptor FLVCR1 J. Virol., February 15, 2006; 80(4): 1742 - 1751. [Abstract] [Full Text] [PDF]

				P. Bottger and L. Pedersen The Central Half of Pit2 Is Not Required for Its Function as a Retroviral Receptor J. Virol., September 1, 2004; 78(17): 9564 - 9567. [Abstract] [Full Text] [PDF]

				I. Knerr, B. Huppertz, C. Weigel, J. Dotsch, C. Wich, R.L. Schild, M.W. Beckmann, and W. Rascher Endogenous retroviral syncytin: compilation of experimental research on syncytin and its possible role in normal and disturbed human placentogenesis Mol. Hum. Reprod., August 1, 2004; 10(8): 581 - 588. [Abstract] [Full Text] [PDF]

				M. Marin, D. Lavillette, S. M. Kelly, and D. Kabat N-Linked Glycosylation and Sequence Changes in a Critical Negative Control Region of the ASCT1 and ASCT2 Neutral Amino Acid Transporters Determine Their Retroviral Receptor Functions J. Virol., March 1, 2003; 77(5): 2936 - 2945. [Abstract] [Full Text] [PDF]