Cloning and Functional Expression of a Brain Peptide/Histidine Transporter

Yamashita, Toshio; Shimada, Shoichi; Guo, Wenlei; Sato, Kohji; Kohmura, Eiji; Hayakawa, Tõru; Takagi, Tsutomu; Tohyama, Masaya

doi:10.1074/jbc.272.15.10205

Cited by 201 publications

(180 citation statements)

References 25 publications

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“…Northern blot hybridization with a 32 P-labeled DBZ cDNA fragment was performed on a human Multiple Tissue Northern Blot filter (Clontech) as described previously. 24 In situ hybridization cDNA fragments of rat DBZ and rat PAC 1 receptor were amplified by RT-PCR (the oligonucleotide primers were 5 0 -CTT TGC GCA GCT GAC TCA GAA-3 0 (sense) and 5 0 -TTC AGC ACT GCG ATC ATT TCC-3 0 (antisense) for rat DBZ, and 5 0 -CTT GTA CAG AAG CTG CAG TC-3 0 (sense) and 5 0 -GGT GCT TGA AGT CCA TAG TG-3 0 (antisense) for rat PAC 1 receptor) and used as templates for probe synthesis. In situ hybridization of sagittal and coronal rat brain sections with 35 S-labeled RNA probes was performed as described previously.…”

Section: Northern Blot Analysismentioning

confidence: 99%

A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth

et al. 2007

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Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a (1;11) (q42.1;q14.3) translocation that segregates with major psychiatric disorders in a Scottish family. To investigate how DISC1 confers susceptibility to psychiatric disorders, we previously identified fasciculation and elongation protein zeta-1 and Kendrin as DISC1-interacting molecules in a yeast twohybrid screen of a human brain complementary DNA library. Here, we have further identified a novel DISC1-interacting protein, termed DISC1-Binding Zinc-finger protein (DBZ), which has a predicted C 2 H 2 -type zinc-finger motif and coiled-coil domains. DBZ was co-immunoprecipitated with DISC1 in lysates of PC12 cells and rat brain tissue. The domain of DISC1 interacting with DBZ was close to the translocation breakpoint in the DISC1 gene. DBZ messenger RNA (mRNA) was expressed in human brains, but not in peripheral tissues. In situ hybridization revealed high expression of DBZ mRNA in the hippocampus, olfactory tubercle, cerebral cortex and striatum in rats. Because this pattern of localization was similar to that of the pituitary adenylate cyclase (PAC 1 ) receptor for pituitary adenylate cyclase-activating polypeptide (PACAP), which has recently been implicated in neuropsychological functions, we examined whether DISC1/DBZ interaction was involved in the PACAP signaling pathway. PACAP upregulated DISC1 expression and markedly reduced the association between DISC1 and DBZ in PC12 cells. A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons. The present results provide some new molecular insights into the mechanisms of neuronal development and neuropsychiatric disorders.

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Section: Northern Blot Analysismentioning

confidence: 99%

A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth

et al. 2007

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“…RnPHT1, expressed in rat brain, exhibits highaffinity dipeptide and high-affinity histidine transport activity (K His m is about 20 lM), but no transport activity can be detected for other amino acids [51]. BnNRT1-2 from Brassica transports nitrate and histidine with similar K m s (both in the mM range), but different pH dependencies [17].…”

Section: Other Substrates and Potential Substrates Of The Nrt1(ptr) Tmentioning

confidence: 99%

Nitrate transporters and peptide transporters

et al. 2007

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In higher plants, two types of nitrate transporters, NRT1 and NRT2, have been identified. In Arabidopsis, there are 53 NRT1 genes and 7 NRT2 genes. NRT2 are high-affinity nitrate transporters, while most members of the NRT1 family are low-affinity nitrate transporters. The exception is CHL1 (AtNRT1.1), which is a dual-affinity nitrate transporter, its mode of action being switched by phosphorylation and dephosphorylation of threonine 101. Two of the NRT1 genes, CHL1 and AtNRT1.2, and two of the NRT2 genes, AtNRT2.1 and AtNRT2.2, are known to be involved in nitrate uptake. In addition, AtNRT1.4 is required for petiole nitrate storage. On the other hand, some members of the NRT1 family are dipeptide transporters, called PTRs, which transport a broad spectrum of di/tripeptides. In barley, HvPTR1, expressed in the plasma membrane of scutellar epithelial cells, is involved in mobilizing peptides, produced by hydrolysis of endosperm storage protein, to the developing embryo. In higher plants, there is another family of peptide transporters, called oligopeptide transporters (OPTs), which transport tetra/pentapeptides. In addition, some OPTs transport GSH, GSSH, GSH conjugates, phytochelatins, and metals.

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“…This compartmentation could also prevent a premature osmotically induced swelling and rupture of lysosomes (75). The question of whether the lysosomal peptide transporter is PEPT1 or one of the PHT histidine/peptide transporters recently cloned, which are found in lysosomes when expressed heterologously (33,55,74), or a completely new transporter remains to be determined.…”

Section: Integrating the Peptide Transporters Into Overall Amino Acidmentioning

confidence: 99%

An update on renal peptide transporters

Daniel

Rubio‐Aliaga

2003

American Journal of Physiology-Renal Physiology

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Daniel, Hannelore, and Isabel Rubio-Aliaga. An update on renal peptide transporters. Am J Physiol Renal Physiol 284: F885-F892, 2003; 10.1152/ajprenal.00123.2002The brush-border membrane of renal epithelial cells contains PEPT1 and PEPT2 proteins that are rheogenic carriers for short-chain peptides. The carrier proteins display a distinct surface expression pattern along the proximal tubule, suggesting that initially di-and tripeptides, either filtered or released by surface-bound hydrolases from larger oligopeptides, are taken up by the low-affinity but high-capacity PEPT1 transporter and then by PEPT2, which possesses a higher affinity but lower transport capacity. Both carriers transport essentially all possible di-and tripeptides and numerous structurally related drugs. A unique feature of the mammalian peptide transporters is the capability of proton-dependent electrogenic cotransport of all substrates, regardless of their charge, that is achieved by variable coupling in proton movement along with the substrate down the transmembrane potential difference. This review focuses on the postcloning research efforts to understand the molecular physiology of peptide transport processes in renal tubules and summarizes available data on the underlying genes, protein structures, and transporter function as derived from studies in heterologous expression systems. PEPT1; PEPT2; renal physiology; localization; functional analysis RENAL TUBULAR PEPTIDE TRANSPORT activity was originally discovered after intravenous infusion of the resistant dipeptide Gly-Sar in rats that resulted in a high accumulation of the intact dipeptide in renal tissue (1, 3). Studies with renal brush-border membrane vesicles established that renal apical peptide uptake was an electrogenic, proton-dependent uphill transport process for di-and tripeptides and related drugs mediated by two kinetically different systems (for a review, see Ref. 38). The underlying proteins, differing in transport characteristics, now designated as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), have been identified, and the corresponding genes have been cloned from a variety of species (10,24,25,39,41,(52)(53)(54). The transporters have been expressed in various cellular models, and information on structure, transport function, and regulation has been gathered by flux studies and electrophysiological techniques. Expression analysis of transporter mRNA and protein by in situ hybridization and immunohistochemistry has extended our knowledge of tissue distribution, particularly the renal zonation of PEPT1 and PEPT2 surface expression. THE MOLECULAR ENTITIES OF APICAL PEPTIDE TRANSPORTPEPT1 and PEPT2 are polytopic integral membrane proteins with 12 predicted membrane-spanning domains and NH 2 -and COOH-terminal ends facing the cytosol. Transporter architecture and membrane topology have not been studied systematically, and therefore structural information is still mainly based on hydropathic analysis of amino acid sequences. The mammalian PEPT1 proteins comprise 701-710 amino acids, ...

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Cloning and Functional Expression of a Brain Peptide/Histidine Transporter

Cited by 201 publications

References 25 publications

A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth

A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth

Nitrate transporters and peptide transporters

An update on renal peptide transporters

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