A novel mitochondrial Ca2+-dependent solute carrier in the liver identified by mRNA differential display.
Pancreatic AR42J cells have the feature of pluripotency of the precursor cells of the gut endoderm. Dexamethasone converts them to exocrine cells or liver cells. Using mRNA differential display techniques, we have identified a novel Ca2+-dependent member of the mitochondrial solute carrier superfamily, which is expressed during the course of differentiation, and have designated it MCSC. The corresponding cDNA comprises an open reading frame of 1407 base pairs encoding a polypeptide of 469 amino acids. The carboxyl-terminal-half of MCSC has high similarity with other mitochondrial carriers, and the amino-terminal-half has three canonical elongation factor-hand motifs and has calcium binding capacity. The deduced amino acid sequence revealed 79.1% homology to the rabbit peroxisomal Ca2+-dependent member of the mitochondrial superfamily, but the subcellular localization of the protein was exclusively mitochondrial, not peroxisomal. Northern blot and Western blot analyses revealed its predominant expression in the liver and the skeletal muscle. In the liver, the expression level of MCSC was higher in the adult stage than in the fetal stage, and MCSC was highly up-regulated in dexamethasone-treated AR42J cells before the expression of albumin. Taken together, MCSC may play an important role in regulating the function of hepatocytes rather than in differentiation in vivo.
Mashima
Hirosato
H
Department of Gastroenterology, University of Tokyo School of Medicine, Tokyo 113-8655, Japan. hmashima1-tky@umin.ac.jp
Ueda
Namiki
N
Ohno
Hideki
H
Suzuki
Junko
J
Ohnishi
Hirohide
H
Yasuda
Hiroshi
H
Tsuchida
Tomohiro
T
Kanamaru
Chiho
C
Makita
Noriko
N
Iiri
Taro
T
Omata
Masao
M
Kojima
Itaru
I
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005938:Glucocorticoids / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D005938:Glucocorticoids; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C473774:Slc25a25 protein, rat; D003907:Dexamethasone; D002118:Calcium