scholarly journals Mutations of the basic amino acid transporter gene associated with cystinuria

1995 ◽  
Vol 310 (3) ◽  
pp. 951-955 ◽  
Author(s):  
K Miyamoto ◽  
K Katai ◽  
S Tatsumi ◽  
K Sone ◽  
H Segawa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Basic Amino Acid ◽  
Amino Acid Transporter ◽  
Regulatory Subunit ◽  
Acid Transport ◽  
Transport Activity ◽  
Wild Type ◽  
Neutral Amino Acid Transporter ◽  
Acid Transporter

To investigate the function of a basic and neutral amino acid transporter-like protein (rBAT) which is a candidate gene for cystinuria, we analysed the rBAT gene in cystinuric patients. Patient 1 is a compound heterozygote with mutations in the rBAT gene causing a glutamine-to-lysine transition at amino acid 268, and a threonine-to-alanine transition at amino acid 341, who inherited these alleles from his mother (E268K) and father (T341A), respectively. Injection of T341A and E268K mutant cRNAs into oocytes decreased transport activity to 53.9% and 62.5% of control (L-cystine transport activity in oocytes injected with wild-type rBAT cRNA), respectively. Co-injection of E268K and T341A into oocytes strongly decreased amino acid transport activity to 28% of control. On the other hand, co-injection of wild-type and mutant rBAT did not decrease transport activity. Furthermore, immunological studies have demonstrated that the reduction of amino acid transport is not due to a decrease in the amount of rBAT protein expressed in oocyte membranes. These results indicate that mutations in the rBAT gene are crucial disease-causing lesions in cystinuria. In addition, co-injection experiments suggest that rBAT may function as a transport activator or regulatory subunit by homo- or hetero-multimer complex formation.

scholarly journals Amino acid sensing by enteroendocrine STC-1 cells: role of the Na+-coupled neutral amino acid transporter 2

2010 ◽  
Vol 298 (6) ◽  
pp. C1401-C1413 ◽  
Author(s):  
Steven H. Young ◽  
Osvaldo Rey ◽  
Catia Sternini ◽  
Enrique Rozengurt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Isobutyric Acid ◽  
Amino Acid Transporter ◽  
Membrane Depolarization ◽  
Neutral Amino Acid ◽  
Acid Transport ◽  
Neutral Amino Acid Transporter ◽  
Acid Transporter

The results presented here show that STC-1 cells, a model of intestinal endocrine cells, respond to a broad range of amino acids, including l-proline, l-serine, l-alanine, l-methionine, l-glycine, l-histidine, and α-methyl-amino-isobutyric acid (MeAIB) with a rapid increase in the intracellular Ca2+ concentration ([Ca2+]i). We sought to identify the mechanism by which amino acids induce Ca2+ signaling in these cells. Several lines of evidence suggest that amino acid transport through the Na+-coupled neutral amino acid transporter 2 (SNAT2) is a major mechanism by which amino acids induced Ca2+ signaling in STC-1 cells: 1) the amino acid efficacy profile for inducing Ca2+ signaling in STC-1 cells closely matches the amino acid specificity of SNAT2; 2) amino acid-induced Ca2+ signaling in STC-1 cells was suppressed by removing Na+ from the medium; 3) the nonmetabolized synthetic substrate of amino acid transport MeAIB produced a marked increase in [Ca2+]i; 4) transfection of small interfering RNA targeting SNAT2 produced a marked decrease in Ca2+ signaling in response to l-proline in STC-1 cells; 5) amino acid-induced increase in [Ca2+]i was associated with membrane depolarization and mediated by Ca2+ influx, since it depended on extracellular Ca2+; 6) the increase in [Ca2+]i in response to l-proline, l-alanine, or MeAIB was abrogated by either nifedipine (1–10 μM) or nitrendipine (1 μM), which block L-type voltage-sensitive Ca2+ channels. We hypothesize that the inward current of Na+ associated with the function of SNAT2 leads to membrane depolarization and activation of voltage-sensitive Ca2+ channels that mediate Ca2+ influx, thereby leading to an increase in the [Ca2+]i in enteroendocrine STC-1 cells.

scholarly journals Effects of Truncation of the COOH-terminal Region of a Na+-independent Neutral and Basic Amino Acid Transporter on Amino Acid Transport inXenopusOocytes

1996 ◽  
Vol 271 (28) ◽  
pp. 16758-16763 ◽  
Author(s):  
Ken-ichi Miyamoto ◽  
Hiroko Segawa ◽  
Sawako Tatsumi ◽  
Kanako Katai ◽  
Hironori Yamamoto ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Basic Amino Acid ◽  
Amino Acid Transporter ◽  
Terminal Region ◽  
Acid Transport ◽  
Acid Transporter

scholarly journals Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle

2014 ◽  
Vol 116 (11) ◽  
pp. 1353-1364 ◽  
Author(s):  
P. T. Reidy ◽  
D. K. Walker ◽  
J. M. Dickinson ◽  
D. M. Gundermann ◽  
M. J. Drummond ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Whey Protein ◽  
Amino Acid Transport ◽  
Amino Acid Transporter ◽  
Acid Transport ◽  
Amino Acid Availability ◽  
Acid Transporter ◽  
Dairy Protein ◽  
Myofibrillar Protein Synthesis

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups ( P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein ( P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein.

scholarly journals Luminal Heterodimeric Amino Acid Transporter Defective in Cystinuria

1999 ◽  
Vol 10 (12) ◽  
pp. 4135-4147 ◽  
Author(s):  
Rahel Pfeiffer ◽  
Jan Loffing ◽  
Grégoire Rossier ◽  
Christian Bauch ◽  
Christian Meier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Autosomal Recessive ◽  
Chromosomal Localization ◽  
Amino Acid Transporter ◽  
Type I ◽  
Acid Transport ◽  
Fusion Construct ◽  
Dibasic Amino Acid ◽  
Acid Transporter

Mutations of the glycoprotein rBAT cause cystinuria type I, an autosomal recessive failure of dibasic amino acid transport (b0,+ type) across luminal membranes of intestine and kidney cells. Here we identify the permease-like protein b0,+AT as the catalytic subunit that associates by a disulfide bond with rBAT to form a hetero-oligomeric b0,+amino acid transporter complex. We demonstrate its b0,+-type amino acid transport kinetics using a heterodimeric fusion construct and show its luminal brush border localization in kidney proximal tubule. These biochemical, transport, and localization characteristics as well as the chromosomal localization on 19q support the notion that the b0,+AT protein is the product of the gene defective in non-type I cystinuria.

scholarly journals The Arabidopsis L-Type Amino Acid Transporter 5 (LAT5/PUT5) Is Expressed in the Phloem and Alters Seed Nitrogen Content When Knocked Out

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1519
Author(s):  
Rowshon A. Begam ◽  
Jayne D’Entremont ◽  
Allen Good
Keyword(s):  
Amino Acid ◽  
Nitrogen Content ◽  
Amino Acid Transport ◽  
Amino Acid Transporter ◽  
Acid Transport ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Wide Range ◽  
Acid Transporter

The Arabidopsis L-type Amino Acid Transporter-5 (LAT5; At3g19553) was recently studied for its role in developmental responses such as flowering and senescence, under an assumption that it is a polyamine uptake transporter (PUT5). The LATs in Arabidopsis have a wide range of substrates, including amino acids and polyamines. This report extensively studied the organ and tissue-specific expression of the LAT5/PUT5 and investigated its role in mediating amino acid transport. Organ-specific quantitative RT-PCR detected LAT5/PUT5 transcripts in all organs with a relatively higher abundance in the leaves. Tissue-specific expression analysis identified GUS activity in the phloem under the LAT5/PUT5 promoter. In silico analysis identified both amino acid transporter and antiporter domains conserved in the LAT5/PUT5 protein. The physiological role of the LAT5/PUT5 was studied through analyzing a mutant line, lat5-1, under various growth conditions. The mutant lat5-1 seedlings showed increased sensitivity to exogenous leucine in Murashige and Skoog growth medium. In soil, the lat5-1 showed reduced leaf growth and altered nitrogen content in the seeds. In planta radio-labelled leucine uptake studies showed increased accumulation of leucine in the lat5-1 plants compared to the wild type when treated in the dark prior to the isotopic feeding. These studies suggest that LAT5/PUT5 plays a role in mediating amino acid transport.

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