Serinc, an activity-regulated protein family, incorporates serine into membrane lipid synthesis.
Cell membranes contain various transporter proteins, some of which are responsible for transferring amino acids across membrane. In this study, we report another class of carrier proteins, termed Serinc1-5, that incorporates a polar amino acid serine into membranes and facilitates the synthesis of two serine-derived lipids, phosphatidylserine and sphingolipids. Serinc is a unique protein family that shows no amino acid homology to other proteins but is highly conserved among eukaryotes. The members contain 11 transmembrane domains, and rat Serinc1 protein co-localizes with lipid biosynthetic enzymes in endoplasmic reticulum membranes. A Serinc protein forms an intracellular complex with key enzymes involved in serine and sphingolipid biosyntheses, and both functions, serine synthesis and membrane incorporation, are linked to each other. In the rat brain, expression of Serinc1 and Serinc2 mRNA was rapidly up-regulated by kainate-induced seizures in neuronal cell layers of the hippocampus. In contrast, myelin throughout the brain is enriched with Serinc5, which was down-regulated in the hippocampus by seizures. These results indicate a novel mechanism linking neural activity and lipid biosynthesis.
Inuzuka
Madoka
M
Department of Neurophysiology, Brain Research Institute, Niigata University, 1 Asahi-machi, Niigata, 951-8585, Japan.
Hayakawa
Minako
M
Ingi
Tatsuya
T
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002855:Chromatography, Thin Layer; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry*; D013107:Sphingolipids / Q000737:chemistry; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
D026921:Amino Acid Transport Systems, Neutral; D018076:DNA, Complementary; D008055:Lipids; D010718:Phosphatidylserines; D011506:Proteins; D012333:RNA, Messenger; D013107:Sphingolipids; D012694:Serine; D007608:Kainic Acid