title: l(2)01810 is a novel type of glutamate transporter that is responsible for megamitochondrial formation.
abstract: l(2)01810 causes glutamine-dependent megamitochondrial formation when it is overexpressed in Drosophila cells. In the present study, we elucidated the function of l(2)01810 during megamitochondrial formation. The overexpression of l(2)01810 and the inhibition of glutamine synthesis showed that l(2)01810 is involved in the accumulation of glutamate. l(2)01810 was predicted to contain transmembrane domains and was found to be localized to the plasma membrane. By using (14)C-labelled glutamate, l(2)01810 was confirmed to uptake glutamate into Drosophila cells with high affinity (K(m)=69.4 μM). Also, l(2)01810 uptakes glutamate in a Na(+)-independent manner. Interestingly, however, this uptake was not inhibited by cystine, which is a competitive inhibitor of Na(+)-independent glutamate transporters, but by aspartate. A signal peptide consisting of 34 amino acid residues targeting to endoplasmic reticulum was predicted at the N-terminus of l(2)01810 and this signal peptide is essential for the protein's localization to the plasma membrane. In addition, l(2)01810 has a conserved functional domain of a vesicular-type glutamate transporter, and Arg(146) in this domain was found to play a key role in glutamate transport and megamitochondrial formation. These results indicate that l(2)01810 is a novel type of glutamate transporter and that glutamate uptake is a rate-limiting step for megamitochondrial formation.
authors: Laboratory of Molecular Genetics and Genomics, School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
authors: Myoung Sup
authors: MS
authors: Shim
authors: Jin Young
authors: JY
authors: Kim
authors: Kwang Hee
authors: KH
authors: Lee
authors: Hee Kyoung
authors: HK
authors: Jung
authors: Bradley A
authors: BA
authors: Carlson
authors: Xue-Ming
authors: XM
authors: Xu
authors: Dolph L
authors: DL
authors: Hatfield
authors: Byeong Jae
authors: BJ
authors: Lee
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000145:classification / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004330:Drosophila; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000502:physiology*; D016297:Mutagenesis, Site-Directed
chemical_list: D027322:Amino Acid Transport System X-AG