scholarly journals Tadr Is an Axonal Histidine Transporter Required for Visual Neurotransmission in Drosophila

2021 ◽  
Author(s):  
Yongchao Han ◽  
Lei Peng ◽  
Tao Wang
Keyword(s):  
Amino Acid ◽  
Synaptic Transmission ◽  
Histidine Decarboxylase ◽  
De Novo ◽  
Critical Role ◽  
Amino Acid Transporter ◽  
Monoamine Neurotransmitter ◽  
Monoamine Neurotransmitters ◽  
Specific Amino Acid ◽  
Acid Transporter

AbstractNeurotransmitters are generated by de novo synthesis and are essential for sustained, high-frequency synaptic transmission. Histamine, a monoamine neurotransmitter, is synthesized through decarboxylation of histidine by Histidine decarboxylase (Hdc). However, little is known about how histidine is presented to Hdc as a precursor. Here, we identified a specific histidine transporter, TADR (Torn And Diminished Rhabdomeres), that is required for visual transmission in Drosophila. TADR and Hdc co-localized to neuronal terminals, and mutations in tadr reduced levels of histamine, thus disrupting visual synaptic transmission and phototaxis behavior. These results demonstrate that a specific amino acid transporter provides precursors for monoamine neurotransmitters, providing the first genetic evidence that a histidine amino acid transporter plays a critical role in synaptic transmission. These results suggest that TADR-dependent local de novo synthesis of histamine is required for synaptic transmission.

scholarly journals Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

2021 ◽  
Vol 22 (4) ◽  
pp. 1707
Author(s):  
Sebastian Granitzer ◽  
Raimund Widhalm ◽  
Martin Forsthuber ◽  
Isabella Ellinger ◽  
Gernot Desoye ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
De Novo ◽  
Structural Similarity ◽  
Amino Acid Transporter ◽  
Cell Number ◽  
Mehg Exposure ◽  
Acid Transporter ◽  
And Oxidative Stress

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

scholarly journals Tissue-Specific Amino Acid Transporter Partners ACE2 and Collectrin Differentially Interact With Hartnup Mutations

2009 ◽  
Vol 136 (3) ◽  
pp. 872-882.e3 ◽  
Author(s):  
Simone M.R. Camargo ◽  
Dustin Singer ◽  
Victoria Makrides ◽  
Katja Huggel ◽  
Klaas M. Pos ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporter ◽  
Specific Amino Acid ◽  
Tissue Specific ◽  
Acid Transporter

Conserved tyrosine-147 plays a critical role in the ligand-gated current of the epithelial cation/amino acid transporter/channel CAATCH1

2002 ◽  
Vol 205 (16) ◽  
pp. 2545-2553 ◽  
Author(s):  
Bruce R. Stevens ◽  
Daniel H. Feldman ◽  
Zhilin Liu ◽  
William R. Harvey
Keyword(s):  
Amino Acid ◽  
Critical Role ◽  
Amino Acid Transporter ◽  
Ionic Channel ◽  
Wild Type ◽  
Channel Conductance ◽  
Current Voltage ◽  
In The Wild ◽  
Inward Currents ◽  
Acid Transporter

SUMMARYCAATCH1 functions both as an amino-acid-gated cation channel and as a cation-dependent, proline-preferring, nutrient amino acid transporter in which the two functions are thermodynamically uncoupled. This study focuses on the ionic channel aspect, in which a Tyr147 (wild type) to Phe147 (Y147F) site-directed mutation was investigated by steady-state electrophysiological measurements in the Xenopus laevisoocyte expression system. This tyrosine residue is conserved within the third transmembrane domain in members of the Na+:neurotransmitter transporter family (SNF), where it plays a role in binding pharmacological ligands such as cocaine to the serotonin (SERT), dopamine (DAT) and norepinephrine (NET) transporters. Epithelial CAATCH1 is a member of the SNF family. The results show that amino acid ligand-gating selectivity and current magnitudes in Na+- and K+-containing media are differentially altered in CAATCH1 Y147F compared with the wild type. In the absence of amino acid ligands, the channel conductance of Na+,K+ and Li+ that is observed in the wild type was reduced to virtually zero in Y147F. In the wild type, proline binding increased conductance strongly in Na+-containing medium and moderately in K+-containing medium, whereas in Y147F proline failed to elicit any cation currents beyond those of N-methyl-D-glucamine- or water-injected oocytes. In the wild type, methionine binding strongly inhibited inward Na+ currents, whereas in Y147F it strongly stimulated inward currents in both Na+ and K+-containing media. Indeed, in Na+-containing medium, the relative potency ranking for inward current inhibition in the wild type(Met>Leu>Gly>Phe>Thr) was similar to the ranking of ligand-permissive gating of large inward currents in Y147F. In Na+-containing medium, current/voltage relationships elicited by ligands in the wild type were complex and reversing, whereas in Y147F they were linear and inwardly rectifying. In K+-containing medium,current/voltage relationships remained non-linear in Y147F. Both wild-type and Y147F currents were Cl--independent. Together, these data demonstrate a critical role for Tyr147 in ligand-binding selectivity and modulation of the ionic channel conductance in CAATCH1. The results support the argument that inhibition of the CAATCH1 conductance by free methionine shares some properties in common with ligand inhibition of DAT, SERT, NET and the γ-aminobutyric acid transporter (GAT1).

N-Glycosylation influences transport, but not cellular trafficking, of a neuronal amino acid transporter SNAT1

2016 ◽  
Vol 473 (22) ◽  
pp. 4227-4242
Author(s):  
Rugmani Padmanabhan Iyer ◽  
Sumin Gu ◽  
Jean X. Jiang
Keyword(s):  
Amino Acid ◽  
De Novo ◽  
Amino Acid Transporter ◽  
Cellular Functions ◽  
Important Amino Acid ◽  
Neutral Amino Acid Transporter ◽  
Glycosylation Sites ◽  
Confocal Immunofluorescence ◽  
Acid Transporter ◽  
Wild Type Control

SNAT1 is a system N/A neutral amino acid transporter that primarily expresses in neurons and mediates the transport of l-glutamine (Gln). Gln is an important amino acid involved in multiple cellular functions and also is a precursor for neurotransmitters, glutamate and GABA. In the present study, we demonstrated that SNAT1 is an N-glycoprotein expressed in neurons. We identified three glycosylation sites at asparagine residues 251, 257 and 310 in SNAT1 protein, and that the first two are the primary sites. The biotinylation and confocal immunofluorescence analysis showed that the glycosylation-impaired mutants and deglycosylated SNAT1 were equally capable of expressing on the cell surface. However, l-Gln and 3H-labeled methyl amino isobutyrate (MeAIB) was significantly compromised in N-glycosylation-impaired mutants and deglycosylated SNAT1 when compared with the wild-type control. Taken together, these results suggest that SNAT1 is an N-glycosylated protein with three de novo glycosylation sites and N-glycosylation of SNAT1 may play an important role in the transport of substrates across the cell membrane.

scholarly journals Protein kinase C activation upregulates human L-type amino acid transporter 2 function

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hanae Morio ◽  
Yoshie Reien ◽  
Yuri Hirayama ◽  
Hirofumi Hashimoto ◽  
Naohiko Anzai
Keyword(s):  
Protein Kinase C ◽  
Amino Acid ◽  
Protein Kinase ◽  
De Novo ◽  
Amino Acid Transporter ◽  
Regulation System ◽  
Membrane Insertion ◽  
Kinase C ◽  
Acid Transporter ◽  
Pkc Activation

AbstractL-type amino acid transporter 2 (LAT2) is a Na+-independent neutral amino acid transporter, whose function regulation system remains unclarified. Since protein kinase C (PKC) is known to regulate the functions of various transporters, we investigated whether human LAT2 (hLAT2) function is regulated by PKC. In mouse proximal tubule S2 cells, hLAT2 transport activity was upregulated by PKC activation. However, we found that the mRNA and protein expression of hLAT2 was not affected by PKC activation and that the upregulation was independent of the three potential PKC consensus sites in the hLAT2 amino acid sequence. Moreover, we found that PKC activation upregulated the Vmax value for hLAT2-mediated alanine transport, which was not accompanied by the induction of hLAT2 membrane insertion. In conclusion, we showed that hLAT2 function is upregulated by PKC activation, which is not related to either the de novo synthesis, the phosphorylation or the membrane insertion of hLAT2.

scholarly journals Transport of Methylmercury through the Epithelial Type Amino Acid Transporter System B0

2019 ◽  
Vol 5 (2) ◽  
pp. 127-136
Author(s):  
Rafiqul Islam ◽  
Naohiko Anzai ◽  
Nesar Ahmed ◽  
Mohammad Ahtashamul Haque ◽  
Shamima Ferdous ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Molecular Mechanism ◽  
Xenopus Oocytes ◽  
Critical Role ◽  
Amino Acid Transporter ◽  
Intestinal Lumen ◽  
Dependent Manner ◽  
Sodium Dependent ◽  
Acid Transporter

Background: System B0 is a sodium dependent transporter that transports wide variety of neutral amino acids in the intestinal and renal proximal tubular epithelial cells. Methylmercury (MeHg) readily and non-enzymatically reacts with cysteine to form conjugate structurally similar to the amino acid methionine. Objective: In this study, we investigated the molecular mechanism of absorptive transport of MeHg in intestine using Xenopus oocytes expressing hB0AT1 and the uptake of metylmercry-Cys (MeHg-Cys) by heterodimeric amino acids transporter. Methodology: We confirmed the uptake of [14C] L-Leucine a potent substrate for the hB0AT1 amino acids transporter. The uptake of [14C] L-leucine by hB0AT1 was inhibited by MeHg-Cys conjugate, leucine, cysteine, methinine and phenylalanine in concentration–dependent manner. The IC50 of MeHg-Cys conjugate was significantly lower than that of leucine, cysteine, methinine and phenylalanine, indicating that hB0AT1 is a high affinity MeHg transporter. To assess MeHg-Cys conjugate transport, we measured [14C] MeHg uptake in Xenopus oocytes expressing hB0AT1 in presence or absence of sodium. The [14C] MeHg was transport only in the presence of cysteine and the transport was significantly sodium dependent and inhibited by a system B0 inhibitor 2-aminobicyclo-[2,21]- haptane-2-carboxylic acid (BCH). Result: The current findings indicate that hB0AT1 and heterodimeric amino acids absorb MeHg in the form of cysteine conjugate from the intestinal lumen across the brush-border membrane in to the cells and is supposed to be plays a critical role in the pathogenesis of Minamata disease and present results descried a major molecular mechanism by which MeHg is transported across cell membranes and indicate that metal complexes may form a novel class of substrates for amino acid carriers. Conclusion: In this experiment the results also suggest that uptake of Methionine and MeHg-Cys by heterodimeric amino acid transporter is significantly correlated where the uptake of Methionine and MeHg-Cys between heterodimeric amino acid transporter and hB0AT1 is not correlated. Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 127-136

Increased expression of an amino acid transporter LAT1 in healing of acetic acid-induced chronic gastric ulcer in rats

2001 ◽  
Vol 120 (5) ◽  
pp. A153-A153
Author(s):  
S MIYAMOTO ◽  
K KATO ◽  
Y ISHII ◽  
S ASAI ◽  
T NAGAISHI ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Gastric Ulcer ◽  
Amino Acid ◽  
Amino Acid Transporter ◽  
Chronic Gastric Ulcer ◽  
Acid Transporter
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