PMID- 24530433 OWN - NLM STAT- MEDLINE DCOM- 20141203 LR - 20140321 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1557 DP - 2014 Apr 4 TI - PAT4 is abundantly expressed in excitatory and inhibitory neurons as well as epithelial cells. PG - 12-25 LID - S0006-8993(14)00186-3 [pii] LID - 10.1016/j.brainres.2014.02.014 [doi] AB - PAT4, the fourth member of the SLC36/proton dependent amino acid transporter (PAT) family, is a high-affinity, low capacity electroneutral transporter of neutral amino acids like proline and tryptophan. It has also been associated with the function of mTORC1, a complex in the mammalian target of rapamycin (mTOR) pathway. We performed in situ hybridization and immunohistological analysis to determine the expression profile of PAT4, as well as an RT-PCR study on tissue from mice exposed to leucine. We performed a phylogenetic analysis to determine the evolutionary origin of PAT4. The in situ hybridization and the immunohistochemistry on mouse brain sections and hypothalamic cells showed abundant PAT4 expression in the mouse brain intracellularly in both inhibitory and excitatory neurons, partially co-localizing with lysosomal markers and epithelial cells lining the ventricles. Its location in epithelial cells around the ventricles indicates a transport of substrates across the blood brain barrier. Phylogenetic analysis showed that PAT4 belongs to an evolutionary old family most likely predating animals, and PAT4 is the oldest member of that family. CI - Copyright (c) 2014 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Roshanbin, Sahar AU - Roshanbin S AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: Sahar.Roshanbin@neuro.uu.se. FAU - Hellsten, Sofie V AU - Hellsten SV AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: Sofie.Hellsten@neuro.uu.se. FAU - Tafreshiha, Atieh AU - Tafreshiha A AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: atieh.tafreshiha@gmail.com. FAU - Zhu, Yinan AU - Zhu Y AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: zhuyinan0108@gmail.com. FAU - Raine, Amanda AU - Raine A AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: Amanda.raine@medsci.uu.se. FAU - Fredriksson, Robert AU - Fredriksson R AD - Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, SE 75124, Sweden. Electronic address: Robert.Fredriksson@neuro.uu.se. LA - eng PT - Journal Article DEP - 20140214 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Amino Acid Transport Systems) RN - 0 (PAT4 protein, mouse) RN - 0 (RNA, Messenger) RN - GMW67QNF9C (Leucine) SB - IM MH - Amino Acid Transport Systems/genetics/*metabolism MH - Animals MH - Blotting, Western MH - Brain/blood supply/*metabolism MH - Cell Membrane/metabolism MH - Choroid Plexus/*metabolism MH - Epithelial Cells/*metabolism MH - Gene Expression MH - Hippocampus/blood supply/metabolism MH - Hypothalamus/blood supply/metabolism MH - Immunohistochemistry MH - In Situ Hybridization MH - Leucine/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neurons/*metabolism MH - Phylogeny MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction OTO - NOTNLM OT - Amino acid transporter OT - Brain OT - Immunoflourescence OT - Immunohistochemistry OT - In situ hybridization OT - Lysosomal transporter OT - Mouse OT - PAT4 OT - SLC36 OT - SLC36A4 EDAT- 2014/02/18 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/02/18 06:00 PHST- 2014/01/09 00:00 [received] PHST- 2014/02/05 00:00 [accepted] PHST- 2014/02/18 06:00 [entrez] PHST- 2014/02/18 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0006-8993(14)00186-3 [pii] AID - 10.1016/j.brainres.2014.02.014 [doi] PST - ppublish SO - Brain Res. 2014 Apr 4;1557:12-25. doi: 10.1016/j.brainres.2014.02.014. Epub 2014 Feb 14.