scholarly journals First evidence for the presence of amino acid sensing mechanisms in the fish gastrointestinal tract

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica Calo ◽  
Ayelén M. Blanco ◽  
Sara Comesaña ◽  
Marta Conde-Sieira ◽  
Sofia Morais ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gastrointestinal Tract ◽  
Intracellular Signaling ◽  
Metabotropic Glutamate Receptors ◽  
Taste Receptor ◽  
Intragastric Administration ◽  
Amino Acid Receptors ◽  
Amino Acid Sensing

AbstractThis study aimed to characterize amino acid sensing systems in the gastrointestinal tract (GIT) of the carnivorous fish model species rainbow trout. We observed that the trout GIT expresses mRNAs encoding some amino acid receptors described in mammals [calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), and taste receptors type 1 members 1 and 2 (T1r1, T1r2)], while others [taste receptor type 1 member 3 (T1r3) and metabotropic glutamate receptors 1 and 4 (mGlur1, mGlur4)] could not be found. Then, we characterized the response of such receptors, as well as that of intracellular signaling mechanisms, to the intragastric administration of l-leucine, l-valine, l-proline or l-glutamate. Results demonstrated that casr, gprc6a, tas1r1 and tas1r2 mRNAs are modulated by amino acids in the stomach and proximal intestine, with important differences with respect to mammals. Likewise, gut amino acid receptors triggered signaling pathways likely mediated, at least partly, by phospholipase C β3 and β4. Finally, the luminal presence of amino acids led to important changes in ghrelin, cholecystokinin, peptide YY and proglucagon mRNAs and/or protein levels. Present results offer the first set of evidence in favor of the existence of amino acid sensing mechanisms within the fish GIT.

scholarly journals Glutamine-induced signaling pathways via amino acid receptors in enteroendocrine L cell lines

2020 ◽  
Vol 64 (3) ◽  
pp. 133-143 ◽  
Author(s):  
Takumi Nakamura ◽  
Kazuki Harada ◽  
Taichi Kamiya ◽  
Mai Takizawa ◽  
Jim Küppers ◽  
...  
Keyword(s):  
Amino Acid ◽  
Taste Receptor ◽  
Underlying Mechanism ◽  
Receptor Type ◽  
Amino Acid Receptors ◽  
Calcium Sensing ◽  
L Cell ◽  
Intracellular Ca ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), secreted by gastrointestinal enteroendocrine L cells, induces insulin secretion and is important for glucose homeostasis. GLP-1 secretion is induced by various luminal nutrients, including amino acids. Intracellular Ca2+ and cAMP dynamics play an important role in GLP-1 secretion regulation; however, several aspects of the underlying mechanism of amino acid-induced GLP-1 secretion are not well characterized. We investigated the mechanisms underlying the L-glutamine-induced increase in Ca2+ and cAMP intracellular concentrations ([Ca2+]i and [cAMP]i, respectively) in murine enteroendocrine L cell line GLUTag cells. Application of L-glutamine to cells under low extracellular [Na+] conditions, which inhibited the function of the sodium-coupled L-glutamine transporter, did not induce an increase in [Ca2+]i. Application of G protein-coupled receptor family C group 6 member A and calcium-sensing receptor antagonist showed little effect on [Ca2+]i and [cAMP]i; however, taste receptor type 1 member 3 (TAS1R3) antagonist suppressed the increase in [cAMP]i. To elucidate the function of TAS1R3, which forms a heterodimeric umami receptor with taste receptor type 1 member 1 (TAS1R1), we generated TAS1R1 and TAS1R3 mutant GLUTag cells using the CRISPR/Cas9 system. TAS1R1 mutant GLUTag cells exhibited L-glutamine-induced increase in [cAMP]i, whereas some TAS1R3 mutant GLUTag cells did not exhibit L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. These findings suggest that TAS1R3 is important for L-glutamine-induced increase in [cAMP]i and GLP-1 secretion. Thus, TAS1R3 may be coupled with Gs and related to cAMP regulation.

Effect of Intraduodenal Starch Infusion on Net Portal Absorption of Amino Acids in Growing steers Fed Lucerne

1994 ◽  
Vol 1994 ◽  
pp. 28-28
Author(s):  
C.J. Seal ◽  
D.S. Parker ◽  
J.C. MacRae ◽  
G.E. Lobley
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gastrointestinal Tract ◽  
Protein Turnover ◽  
Portal Blood ◽  
Intestinal Lumen ◽  
Short Term ◽  
Net Uptake ◽  
Amino Acid Requirements ◽  
Glucose Availability

Amino acid requirements for energy metabolism and protein turnover within the gastrointestinal tract are substantial and may be met from luminal and arterial pools of amino acids. Several studies have demonstrated that the quantity of amino acids appearing in the portal blood does not balance apparent disappearance from the intestinal lumen and that changing diet or the availability of energy-yielding substrates to the gut tissues may influence the uptake of amino acids into the portal blood (Seal & Reynolds, 1993). For example, increased net absorption of amino acids was observed in animals receiving exogenous intraruminal propionate (Seal & Parker, 1991) and this was accompanied by changes in glucose utilisation by the gut tissues. In contrast, there was no apparent change in net uptake of [l-13C]-leucine into the portal vein of sheep receiving short term intraduodenal infusions of glucose (Piccioli Cappelli et al, 1993). This experiment was designed to further investigate the effects on amino acid absorption of changing glucose availability to the gut with short term (seven hours) or prolonged (three days) exposure to starch infused directly into the duodenum.

scholarly journals Activation of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae Correlates with the Phosphorylation State of a Sensor Component, Ptr3

2007 ◽  
Vol 28 (2) ◽  
pp. 551-563 ◽  
Author(s):  
Zhengchang Liu ◽  
Janet Thornton ◽  
Mário Spírek ◽  
Ronald A. Butow
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Amino Acid ◽  
Nuclear Translocation ◽  
Proteolytic Processing ◽  
Casein Kinase I ◽  
Positive Regulators ◽  
Amino Acid Permeases ◽  
Amino Acid Sensing ◽  
Amino Acid Sensor

ABSTRACT Cells of the budding yeast Saccharomyces cerevisiae sense extracellular amino acids and activate expression of amino acid permeases through the SPS-sensing pathway, which consists of Ssy1, an amino acid sensor on the plasma membrane, and two downstream factors, Ptr3 and Ssy5. Upon activation of SPS signaling, two transcription factors, Stp1 and Stp2, undergo Ssy5-dependent proteolytic processing that enables their nuclear translocation. Here we show that Ptr3 is a phosphoprotein whose hyperphosphorylation is increased by external amino acids and is dependent on Ssy1 but not on Ssy5. A deletion mutation in GRR1, encoding a component of the SCFGrr1 E3 ubiquitin ligase, blocks amino acid-induced hyperphosphorylation of Ptr3. We found that two casein kinase I (CKI) proteins, Yck1 and Yck2, previously identified as positive regulators of SPS signaling, are required for hyperphosphorylation of Ptr3. Loss- and gain-of-function mutations in PTR3 result in decreased and increased Ptr3 hyperphosporylation, respectively. We found that a defect in PP2A phosphatase activity leads to the hyperphosphorylation of Ptr3 and constitutive activation of SPS signaling. Two-hybrid analysis revealed interactions between the N-terminal signal transduction domain of Ssy1 with Ptr3 and Yck1. Our findings reveal that CKI and PP2A phosphatase play antagonistic roles in SPS sensing by regulating Ptr3 phosphorylation.

scholarly journals Mutational Analysis of the Hydrophobic Tail of the Human Immunodeficiency Virus Type 1 p6Gag Protein Produces a Mutant That Fails To Package Its Envelope Protein

1999 ◽  
Vol 73 (1) ◽  
pp. 19-28 ◽  
Author(s):  
David E. Ott ◽  
Elena N. Chertova ◽  
Laura K. Busch ◽  
Lori V. Coren ◽  
Tracy D. Gagliardi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Hydrophobic Tail ◽  
Carboxyl Terminal ◽  
Hiv 1

ABSTRACT The p6Gag protein of human immunodeficiency virus type 1 (HIV-1) is produced as the carboxyl-terminal sequence within the Gag polyprotein. The amino acid composition of this protein is high in hydrophilic and polar residues except for a patch of relatively hydrophobic amino acids found in the carboxyl-terminal 16 amino acids. Internal cleavage of p6Gag between Y36 and P37, apparently by the HIV-1 protease, removes this hydrophobic tail region from approximately 30% of the mature p6Gag proteins in HIV-1MN. To investigate the importance of this cleavage and the hydrophobic nature of this portion of p6Gag, site-directed mutations were made at the minor protease cleavage site and within the hydrophobic tail. The results showed that all of the single-amino-acid-replacement mutants exhibited either reduced or undetectable cleavage at the site yet almost all were nearly as infectious as wild-type virus, demonstrating that processing at this site is not important for viral replication. However, one exception, Y36F, was 300-fold as infectious the wild type. In contrast to the single-substitution mutants, a virus with two substitutions in this region of p6Gag, Y36S-L41P, could not infect susceptible cells. Protein analysis showed that while the processing of the Gag precursor was normal, the double mutant did not incorporate Env into virus particles. This mutant could be complemented with surface glycoproteins from vesicular stomatitis virus and murine leukemia virus, showing that the inability to incorporate Env was the lethal defect for the Y36S-L41P virus. However, this mutant was not rescued by an HIV-1 Env with a truncated gp41TM cytoplasmic domain, showing that it is phenotypically different from the previously described MA mutants that do not incorporate their full-length Env proteins. Cotransfection experiments with Y36S-L41P and wild-type proviral DNAs revealed that the mutant Gag dominantly blocked the incorporation of Env by wild-type Gag. These results show that the Y36S-L41P p6Gag mutation dramatically blocks the incorporation of HIV-1 Env, presumably acting late in assembly and early during budding.

scholarly journals Minireview: Nutrient Sensing by G Protein-Coupled Receptors

2013 ◽  
Vol 27 (8) ◽  
pp. 1188-1197 ◽  
Author(s):  
Eric M. Wauson ◽  
Andrés Lorente-Rodríguez ◽  
Melanie H. Cobb
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
G Protein ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Nutrient Sensing ◽  
G Protein Coupled Receptors ◽  
Amino Acid Availability ◽  
Class C ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are membrane proteins that recognize molecules in the extracellular milieu and transmit signals inside cells to regulate their behaviors. Ligands for many GPCRs are hormones or neurotransmitters that direct coordinated, stereotyped adaptive responses. Ligands for other GPCRs provide information to cells about the extracellular environment. Such information facilitates context-specific decision making that may be cell autonomous. Among ligands that are important for cellular decisions are amino acids, required for continued protein synthesis, as metabolic starting materials and energy sources. Amino acids are detected by a number of class C GPCRs. One cluster of amino acid-sensing class C GPCRs includes umami and sweet taste receptors, GPRC6A, and the calcium-sensing receptor. We have recently found that the umami taste receptor heterodimer T1R1/T1R3 is a sensor of amino acid availability that regulates the activity of the mammalian target of rapamycin. This review focuses on an array of findings on sensing amino acids and sweet molecules outside of neurons by this cluster of class C GPCRs and some of the physiologic processes regulated by them.

Taste Receptors in the Gastrointestinal Tract II.l-Amino acid sensing by calcium-sensing receptors: implications for GI physiology

2006 ◽  
Vol 291 (5) ◽  
pp. G753-G761 ◽  
Author(s):  
Arthur D. Conigrave ◽  
Edward M. Brown
Keyword(s):  
Amino Acid ◽  
Gastrointestinal Tract ◽  
Epithelial Transport ◽  
Hormone Secretion ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Gut Hormone ◽  
Protein Ingestion ◽  
Amino Acid Sensing ◽  
Amino Acid Sensor

The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for several key nutrients, notably Ca2+ions and l-amino acids, and is expressed abundantly throughout the gastrointestinal tract. While its role as a Ca2+ion sensor is well recognized, its physiological significance as an l-amino acid sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion is only now coming to light. This review focuses on the CaR’s amino acid sensing properties at both the molecular and cellular levels and considers new and putative physiological roles for the CaR in the amino acid-dependent regulation of gut hormone secretion, epithelial transport, and satiety.

scholarly journals Dephosphorylation of eIF-2α Mediated by the γ134.5 Protein of Herpes Simplex Virus Type 1 Is Required for Viral Response to Interferon but Is Not Sufficient for Efficient Viral Replication

2003 ◽  
Vol 77 (18) ◽  
pp. 10154-10161 ◽  
Author(s):  
Guofeng Cheng ◽  
Kui Yang ◽  
Bin He
Keyword(s):  
Amino Acids ◽  
Herpes Simplex Virus ◽  
Amino Acid ◽  
Herpes Simplex ◽  
Viral Replication ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Wild Type ◽  
Simplex Virus

ABSTRACT The γ134.5 protein of herpes simplex virus type 1 (HSV-1) functions to block the shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase (PKR). In this process, the γ134.5 protein recruits cellular protein phosphatase 1 (PP1) to form a high-molecular-weight complex that dephosphorylates eIF-2α. Here we show that the γ134.5 protein is capable of mediating eIF-2α dephosphorylation without any other viral proteins. While deletion of amino acids 1 to 52 from the γ134.5 protein has no effect on eIF-2α dephosphorylation, further truncations up to amino acid 146 dramatically reduce the activity of the γ134.5 protein. An additional truncation up to amino acid 188 is deleterious, indicating that the carboxyl-terminal domain alone is not functional. Like wild-type HSV-1, the γ134.5 mutant with a truncation of amino acids 1 to 52 is resistant to interferon, and resistance to interferon is coupled to eIF-2α dephosphorylation. Intriguingly, this mutant exhibits a similar growth defect seen for the γ134.5 null mutant in infected cells. Restoration of the wild-type γ134.5 gene in the recombinant completely reverses the phenotype. These results indicate that eIF-2α dephosphorylation mediated by the γ134.5 protein is required for HSV response to interferon but is not sufficient for viral replication. Additional functions or activities of the γ134.5 protein contribute to efficient viral infection.

scholarly journals Human Immunodeficiency Virus Type 1 Env Sequences from Calcutta in Eastern India: Identification of Features That Distinguish Subtype C Sequences in India from Other Subtype C Sequences

2001 ◽  
Vol 75 (21) ◽  
pp. 10479-10487 ◽  
Author(s):  
Raj Shankarappa ◽  
Ramdas Chatterjee ◽  
Gerald H. Learn ◽  
Dhruba Neogi ◽  
Ming Ding ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Heterosexual Transmission ◽  
Subtype C ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viralenv from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype Cenv, and one had viruses with a subtype Aenv. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate CIN. Overall, CIN lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for CIN sequences (K340E, K350A, and G429E), 56% of the CIN sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-CINsequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

scholarly journals Amino acid sensing and mTOR regulation: inside or out?

2009 ◽  
Vol 37 (1) ◽  
pp. 248-252 ◽  
Author(s):  
Deborah C.I. Goberdhan ◽  
Margret H. Ögmundsdóttir ◽  
Shubana Kazi ◽  
Bruno Reynolds ◽  
Shivanthy M. Visvalingam ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Growth Factor ◽  
Environmental Conditions ◽  
Detection System ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Amino Acid Sensing ◽  
The Impact ◽  
Mtor Signalling

mTOR (mammalian target of rapamycin) plays a key role in determining how growth factor, nutrient and oxygen levels modulate intracellular events critical for the viability and growth of the cell. This is reflected in the impact of aberrant mTOR signalling on a number of major human diseases and has helped to drive research to understand how TOR (target of rapamycin) is itself regulated. While it is clear that amino acids can affect TOR signalling, how these molecules are sensed by TOR remains controversial, perhaps because cells use different mechanisms as environmental conditions change. Even the question of whether they have an effect inside the cell or at its surface remains unresolved. The present review summarizes current ideas and suggests ways in which some of the models proposed might be unified to produce an amino acid detection system that can adapt to environmental change.

scholarly journals Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1

2011 ◽  
Vol 301 (1) ◽  
pp. G128-G137 ◽  
Author(s):  
Anna-Maria Nässl ◽  
Isabel Rubio-Aliaga ◽  
Henning Fenselau ◽  
Mena Katharina Marth ◽  
Gabor Kottra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dietary Protein ◽  
Physiological Role ◽  
Transport Processes ◽  
Peptide Transporter ◽  
Intragastric Administration ◽  
Ussing Chambers ◽  
Acid Absorption ◽  
Amino Acid Absorption

The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1−/−compared with Pept1+/+animals, suggesting that amino acid handling is altered. Plasma appearance rates of15N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism.

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