Cloning and functional characterization of a novel up-regulator, cartregulin, of carnitine transporter, OCTN2.
Acetylcarnitine exerts therapeutic effects on some neurological disorders including Alzheimer's disease. OCTN2 is known as a transporter for acetylcarnitine, but its expression in the brain is very low. To examine a brain-specific transporter for acetylcarnitine, we screened a rat brain cDNA library by hybridization using a DNA probe conserved among an OCTN family. A cDNA homologous to OCTN2 cDNA was isolated. The cDNA encoded a novel 146-amino acid protein with one putative transmembrane domain. The mRNA was expressed not only in rat brain but also in some other tissues. The novel protein was localized in endoplasmic reticulum when expressed in COS-7 cells but exhibited no transport activity for acetylcarnitine. However, when co-expressed with OCTN2, it enhanced the OCTN2-mediated transport by about twofold. The enhancement was accompanied by an increase in the levels of mRNA and protein. When OCTN2 was expressed in Xenopus oocytes by injection of its cRNA, its transport activity was enhanced by co-expression of the novel protein. These data suggest that the novel protein increases OCTN2 by stabilizing the mRNA in endoplasmic reticulum. The protein may be an up-regulator of OCTN2 and is tentatively designated cartregulin.
Nagai
Kazuhiko
K
Department of Pharmacology, Hokkaido University Graduate School of Medicine, N15, W7, Sapporo 060-8638, Japan.
Takikawa
Osamu
O
Kawakami
Naoko
N
Fukao
Mitsuhiro
M
Soma
Takamitsu
T
Oda
Atsushi
A
Nishiya
Tadashi
T
Hayashi
Misato
M
Lu
Lingyun
L
Nakano
Manabu
M
Kajita
Emi
E
Fujita
Hiroyoshi
H
Miwa
Soichi
S
D000108:Acetylcarnitine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000201:enzymology; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000074058:Solute Carrier Family 22 Member 5; D013379:Substrate Specificity; D015854:Up-Regulation
D018076:DNA, Complementary; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; C513316:cartregulin, rat; D000108:Acetylcarnitine