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J. Biol. Chem., Vol. 275, Issue 51, 40064-40072, December 22, 2000
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From the Carnitine is essential for The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AB016257 and AB018436.
Molecular and Functional Characterization of Organic
Cation/Carnitine Transporter Family in Mice*
§,,§,,§
Faculty of Pharmaceutical Sciences, Kanazawa
University, Kanazawa 920-0934, § Core Research for
Evolutional Science and Technology (CREST), Japan Science and
Technology Corp. (JST), Kawaguchi 332-0012, and ¶ Chugai Research
Institute for Molecular Medicine Inc., Ibaraki 300-4101, Japan
-oxidation of fatty
acids, and a defect of cell membrane transport of carnitine leads to
fatal systemic carnitine deficiency. We have already shown that a
defect of the organic cation/carnitine transporter OCTN2 is a primary cause of systemic carnitine deficiency. In the present study, we
further isolated and characterized new members of the OCTN family,
OCTN1 and -3, in mice. All three members were expressed commonly in
kidney, and OCTN1 and -2 were also expressed in various tissues,
whereas OCTN3 was characterized by predominant expression in testis.
When their cDNAs were transfected into HEK293 cells, the cells
exhibited transport activity for carnitine and/or the organic cation
tetraethylammonium (TEA). Carnitine transport by OCTN1 and OCTN2 was
Na+-dependent, whereas that by OCTN3 was
Na+-independent. TEA was transported by OCTN1 and OCTN2 but
not by OCTN3. The relative uptake activity ratios of carnitine to TEA were 1.78, 11.3, and 746 for OCTN1, -2, and -3, respectively, suggesting high specificity of OCTN3 for carnitine and significantly lower carnitine transport activity of OCTN1. Thus, OCTN3 is unique in
its limited tissue distribution and Na+-independent
carnitine transport, whereas OCTN1 efficiently transported TEA with
minimal expression of carnitine transport activity and may have a
different role from other members of the OCTN family.
*
This work was supported in part by a grant-in-aid for
Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan and by a grant from the Japan Health Sciences Foundation Drug Innovation Project.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences, Kanazawa
University, 13-1 Takara-machi, Kanazawa 920-0934, Japan. Tel.:
81-76-234-4479; Fax: 81-76-234-4477; E-mail:
tsuji@kenroku.kanazawa-u.ac.jp.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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