OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2.
A novel organic cation transporter OCTN2 is indispensable for carnitine transport across plasma membrane and subsequent fatty acid metabolism in the mitochondria. Here, we report a novel splice variant of OCTN2 (OCTN2VT), in which a 72-base-pair sequence located in the first intron of OCTN2 gene was spliced between exons 1 and 2 of OCTN2, causing the insertion of 24 amino acids in the first extracellular loop of OCTN2. Despite the similarity between OCTN2 and OCTN2VT regarding primary structure and tissue distribution, their biochemical characteristics were significantly different. OCTN2 was expressed on the plasma membrane with robust N-glycosylation, whereas OCTN2VT was retained in the endoplasmic reticulum (ER) with poor N-glycosylation. In addition, the retention in the ER caused no carnitine uptake into the cells. These results demonstrate that the biochemical and functional characteristics of OCTN2VT are distinct from OCTN2 due to the insertion of 24 amino acids in the first extracellular loop.
Maekawa
Satoshi
S
Department of Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Mori
Daisuke
D
Nishiya
Tadashi
T
Takikawa
Osamu
O
Horinouchi
Takahiro
T
Nishimoto
Arata
A
Kajita
Emi
E
Miwa
Soichi
S
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence / Q000235:genetics; D001692:Biological Transport / Q000502:physiology; D002331:Carnitine / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D000074058:Solute Carrier Family 22 Member 5
D005227:Fatty Acids; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine