ASCT1 and ASCT2: Brother and Sister?

2021 ◽  
pp. 247255522110302
Author(s):  
Mariafrancesca Scalise ◽  
Lara Console ◽  
Jessica Cosco ◽  
Lorena Pochini ◽  
Michele Galluccio ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Physiological Role ◽  
Cell Plasma Membrane ◽  
Substrate Specificities ◽  
High Affinity ◽  
Regulatory Aspects ◽  
Pathological Conditions ◽  
Cell Plasma ◽  
3D Architecture

The SLC1 family includes seven members divided into two groups, namely, EAATs and ASCTs, that share similar 3D architecture; the first one includes high-affinity glutamate transporters, and the second one includes SLC1A4 and SLC1A5, known as ASCT1 and ASCT2, respectively, responsible for the traffic of neutral amino acids across the cell plasma membrane. The physiological role of ASCT1 and ASCT2 has been investigated over the years, revealing different properties in terms of substrate specificities, affinities, and regulation by physiological effectors and posttranslational modifications. Furthermore, ASCT1 and ASCT2 are involved in pathological conditions, such as neurodegenerative disorders and cancer. This has driven research in the pharmaceutical field aimed to find drugs able to target the two proteins. This review focuses on structural, functional, and regulatory aspects of ASCT1 and ASCT2, highlighting similarities and differences.

MYOSTATIN - A MODERN UNDERSTANDING OF THE PHYSIOLOGICAL ROLE AND SIGNIFICANCE IN THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES

2021 ◽  
pp. 701-706
Author(s):  
А.А. Газданова ◽  
В.Г. Кукес ◽  
О.К. Парфенова ◽  
Н.Г. Сидоров ◽  
А.В. Перков ◽  
...  
Keyword(s):  
Muscle Growth ◽  
Physiological Role ◽  
Review Article ◽  
Negative Regulator ◽  
Transforming Growth Factors ◽  
Endogenous Factors ◽  
Pathological Conditions ◽  
Physiological Properties ◽  
The Family

Миостатин - белок, принадлежащий к классу миокинов, семейству трансформирующих факторов роста β (TGF-β). В обзорной статье, анализирующей данные литературы, показана ключевая роль миостатина в развитии старческой саркопении и кахексии при различных патологических состояниях, таких как рак, ХСН, ХБП, ХОБЛ и др. В статье рассматривается структура миостатина, подробная схема синтеза и его активации, механизм действия как негативного регулятора роста и дифференцировки мышц при этих патологических состояниях. Выделены основные физиологические свойства и клиническое значение. Рассмотрены экзогенные и эндогенные факторы, регулирующие экспрессию миостатина, и возможные механизмы их действия. Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

scholarly journals Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus

2015 ◽  
Vol 89 (18) ◽  
pp. 9440-9453 ◽  
Author(s):  
Emmanuel Adu-Gyamfi ◽  
Kristen A. Johnson ◽  
Mark E. Fraser ◽  
Jordan L. Scott ◽  
Smita P. Soni ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Human Cell ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Cell Plasma Membrane ◽  
Replication Process ◽  
Cell Plasma

ABSTRACTLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.IMPORTANCEThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

scholarly journals Update in TSH Receptor Agonists and Antagonists

2012 ◽  
Vol 97 (12) ◽  
pp. 4287-4292 ◽  
Author(s):  
Marvin C. Gershengorn ◽  
Susanne Neumann
Keyword(s):  
Thyroid Function ◽  
Small Molecule ◽  
Physiological Role ◽  
Tsh Receptor ◽  
Thyroid Tumors ◽  
Inverse Agonists ◽  
Small Molecule Drug ◽  
Pathological Conditions ◽  
Receptor Agonists And Antagonists

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands.

Quantitative analysis of aldosterone's role in potassium regulation

1988 ◽  
Vol 255 (5) ◽  
pp. F811-F822 ◽  
Author(s):  
D. B. Young
Keyword(s):  
Quantitative Analysis ◽  
Renal Excretion ◽  
Potassium Concentration ◽  
Physiological Role ◽  
Plasma Potassium ◽  
The Body ◽  
Pharmacological Interventions ◽  
Pathological Conditions ◽  
Potassium Regulation

Aldosterone is part of a complex system that regulates plasma potassium concentration by affecting the renal excretion of the ion as well as its distribution within the body. Because there are other components of the system, it has been difficult to determine the physiological significance of aldosterone in potassium regulation by attempting to study the hormone's effects in isolation. In this presentation a quantitative analysis of the potassium control system is used to provide information concerning the physiological role of aldosterone in potassium regulation under normal and pathological conditions, as well as during pharmacological interventions.

scholarly journals Luminal Ca2+ content regulates intracellular Ca2+ release in subepicardial myocytes of intact beating mouse hearts: effect of exogenous buffers

2010 ◽  
Vol 298 (6) ◽  
pp. H2138-H2153 ◽  
Author(s):  
Dmytro Kornyeyev ◽  
Mariano Reyes ◽  
Ariel L. Escobar
Keyword(s):  
Frequency Dependence ◽  
Ventricular Myocytes ◽  
Heart Beat ◽  
Association Rate ◽  
Intact Mouse ◽  
High Affinity ◽  
Pathological Conditions ◽  
Epicardial Layer ◽  
Major Factors

Ca+-induced Ca2+ release tightly controls the function of ventricular cardiac myocytes under normal and pathological conditions. Two major factors contributing to the regulation of Ca2+ release are the cytosolic free Ca2+ concentration and sarcoplasmic reticulum (SR) Ca2+ content. We hypothesized that the amount of Ca2+ released from the SR during each heart beat strongly defines the refractoriness of Ca2+ release. To test this hypothesis, EGTA AM, a high-affinity, slow-association rate Ca2+ chelator, was used as a tool to modify luminal SR Ca2+ content. An analysis of the cytosolic and luminal SR Ca2+ dynamics recorded from the epicardial layer of intact mouse hearts indicated that the presence of EGTA reduced the diastolic SR free Ca2+ concentration and fraction of SR Ca2+ depletion during each beat. In addition, this maneuver shortened the refractory period and accelerated the restitution of Ca2+ release. As a consequence of the accelerated restitution, the frequency dependence of Ca2+ alternans was significantly shifted toward higher heart rates, suggesting a role of luminal SR Ca2+ in the genesis of this highly arrhythmogenic phenomenon. Thus, intra-SR Ca2+ dynamics set the refractoriness and frequency dependence of Ca2+ transients in subepicardial ventricular myocytes.

scholarly journals Nitrite Transport Activity of the ABC-Type Cyanate Transporter of the Cyanobacterium Synechococcus elongatus

2009 ◽  
Vol 191 (10) ◽  
pp. 3265-3272 ◽  
Author(s):  
Shin-ichi Maeda ◽  
Tatsuo Omata
Keyword(s):  
Nitrogen Deficiency ◽  
Physiological Role ◽  
Synechococcus Elongatus ◽  
Transport Activity ◽  
High Affinity ◽  
Low Concentrations ◽  
Cyanobacterial Species ◽  
Relative Specificity ◽  
Nitrite Transport

ABSTRACT In addition to the ATP-binding cassette (ABC)-type nitrate/nitrite-bispecific transporter, which has a high affinity for both substrates (Km , ∼1 μM), Synechococcus elongatus has an active nitrite transport system with an apparent Km (NO2 −) value of 20 μM. We found that this activity depends on the cynABD genes, which encode a putative cyanate (NCO−) ABC-type transporter. Accordingly, nitrite transport by CynABD was competitively inhibited by NCO− with a Ki value of 0.025 μM. The transporter was induced under conditions of nitrogen deficiency, and the induced cells showed a V max value of 11 to 13 μmol/mg of chlorophyll per h for cyanate or nitrite, which could supply ∼30% of the amount of nitrogen required for optimum growth. Its relative specificity for the substrates and regulation at transcriptional and posttranslational levels suggested that the physiological role of the bispecific cyanate/nitrite transporter in S. elongatus is to allow nitrogen-deficient cells to assimilate low concentrations of cyanate in the medium. Its contribution to nitrite assimilation was significant in a mutant lacking the ABC-type nitrate/nitrite transporter, suggesting a possible role for CynABD in nitrite assimilation by cyanobacterial species that lack another high-affinity mechanism(s) for nitrite transport.

scholarly journals Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1969
Author(s):  
Sonia Levi ◽  
Maddalena Ripamonti ◽  
Marko Dardi ◽  
Anna Cozzi ◽  
Paolo Santambrogio
Keyword(s):  
Physiological Condition ◽  
Physiological Role ◽  
Biochemical Properties ◽  
Cross Reactivity ◽  
Pathological Conditions ◽  
Human Ferritin ◽  
Ferritin Gene ◽  
New Type ◽  
Very High

In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed.

scholarly journals Biochemical evidence for the reversed polarity of the outer membrane of the bacterial forespore

1975 ◽  
Vol 152 (3) ◽  
pp. 561-569 ◽  
Author(s):  
B J Wilkinson ◽  
J A Deans ◽  
D J Ellar
Keyword(s):  
Outer Membrane ◽  
Nadh Dehydrogenase ◽  
Nadh Oxidase ◽  
Permeability Barrier ◽  
Cell Plasma Membrane ◽  
High Affinity ◽  
Cell Plasma ◽  
Membrane Bound ◽  
Reversed Polarity ◽  
Nadh Oxidase Activity

Measurement of certain membrane-bound enzymic activities was used to study the orientation of the outer membrane of the double-membraned forespore of Bacillus megaterium KM. 2. Adenosine triphosphatase, NADH dehydrogenase and L-malate intact protoplasts, but were readily detected in intact stage II or IV forespores, consistent with reversed polarity of the outer forespore membrane relative to the mother-cell plasma membrane. 3. Measurement of NADH oxidase activity revealed that intact stage III forespores had the same high affinity for NADH as protoplast membrane preparations and protoplast lystates, consistent with ready access of NADH to oxidation sites on the outer forespores membrane. 4. Forespores and protoplasts showed osmometric behaviour in solutions of non-permanent solutes consistent with the presence of an intact permeability barrier in these structures.

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