Molecular structure and regulation of vertebrate Na+/H+ exchangers.

1994 ◽  
Vol 196 (1) ◽  
pp. 337-345 ◽  
Author(s):  
L Bianchini ◽  
J Pousségur
Keyword(s):  
Molecular Structure ◽  
Plasma Membrane ◽  
Structure Function ◽  
Cellular Localization ◽  
Molecular Level ◽  
Cellular Functions ◽  
New Gene ◽  
Regulation Mechanisms ◽  
Function Relationship ◽  
Transmembrane Transporters

Na+/H+ exchangers (NHE), also called antiporters, are vital transmembrane transporters involved in multiple cellular functions including the regulation of intracellular pH, the control of cell volume and transepithelial ion transport. These transporters are highly regulated by a remarkably wide variety of stimuli which can modulate their expression level and activity. Five isoforms of Na+/H+ exchangers have been cloned and characterized to date; they define a new gene family of vertebrate transporters. These isoforms share the same overall structure but exhibit differences with respect to amiloride-sensitivity, cellular localization, kinetic variables, regulation by various stimuli and plasma membrane targeting in polarized epithelial cells. Biochemical techniques and molecular genetics tools provide the means of analyzing these transporters at the molecular level. The purpose of this manuscript is to give an overview of the main features of the Na+/H+ exchangers with emphasis on recent advances in comprehension of the structure-function relationship and regulation mechanisms of the ubiquitous isoform: NHE-1.

scholarly journals Molecular structure‐function relationship of dietary polyphenols for inhibiting VEGF‐induced VEGFR‐2 activity

2015 ◽  
Vol 59 (11) ◽  
pp. 2119-2131 ◽  
Author(s):  
Ana B. Cerezo ◽  
Mark S. Winterbone ◽  
Christina W. A. Moyle ◽  
Paul W. Needs ◽  
Paul A. Kroon
Keyword(s):  
Molecular Structure ◽  
Structure Function ◽  
Dietary Polyphenols ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Relationship Of

Caveolae: Structure, Function, and Relationship to Disease

2018 ◽  
Vol 34 (1) ◽  
pp. 111-136 ◽  
Author(s):  
Robert G. Parton
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Structure Function ◽  
Lipid Composition ◽  
Mammalian Cells ◽  
Eukaryotic Cells ◽  
Interacting Proteins ◽  
Endocytic Vesicle ◽  
Cellular Functions

The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.

Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters

1998 ◽  
Vol 78 (4) ◽  
pp. 969-1054 ◽  
Author(s):  
MANUEL PALACÍN ◽  
RAÚL ESTÉVEZ ◽  
JOAN BERTRAN ◽  
ANTONIO ZORZANO
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Molecular Biology ◽  
Structure Function ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Cationic Amino Acid ◽  
Function Relationship

Palacı́n, Manuel, Raúl Estévez, Joan Bertran, and Antonio Zorzano. Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters. Physiol. Rev. 78: 969–1054, 1998. — Molecular biology entered the field of mammalian amino acid transporters in 1990–1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 20 mammalian amino acid transporters. All of them belong to four protein families. Here we describe the tissue expression, transport characteristics, structure-function relationship, and the putative physiological roles of these transporters. Wherever possible, the ascription of these transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of amino acid transport in mammals in the last 3 years, such as the construction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing number of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene ( rBAT) responsible for an inherited disease of amino acid transport (cystinuria) has been identified. Identifying the molecular structure of amino acid transport systems of high physiological relevance (e.g., system A, L, N, and x−c) and of the genes responsible for other aminoacidurias as well as revealing the key molecular mechanisms of the amino acid transporters are the main challenges of the future in this field.

scholarly journals Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Kim Shortall ◽  
Ahmed Djeghader ◽  
Edmond Magner ◽  
Tewfik Soulimane
Keyword(s):  
Structure Function ◽  
Neurological Diseases ◽  
Normal Activity ◽  
Structural Features ◽  
Cellular Functions ◽  
Common Structure ◽  
Structure Function Relationship ◽  
Key Enzyme ◽  
Correct Function ◽  
Function Relationship

Aldehyde dehydrogenases engage in many cellular functions, however their dysfunction resulting in accumulation of their substrates can be cytotoxic. ALDHs are responsible for the NAD(P)-dependent oxidation of aldehydes to carboxylic acids, participating in detoxification, biosynthesis, antioxidant and regulatory functions. Severe diseases, including alcohol intolerance, cancer, cardiovascular and neurological diseases, were linked to dysfunctional ALDH enzymes, relating back to key enzyme structure. An in-depth understanding of the ALDH structure-function relationship and mechanism of action is key to the understanding of associated diseases. Principal structural features 1) cofactor binding domain, 2) active site and 3) oligomerization mechanism proved critical in maintaining ALDH normal activity. Emerging research based on the combination of structural, functional and biophysical studies of bacterial and eukaryotic ALDHs contributed to the appreciation of diversity within the superfamily. Herewith, we discuss these studies and provide our interpretation for a global understanding of ALDH structure and its purpose–including correct function and role in disease. Our analysis provides a synopsis of a common structure-function relationship to bridge the gap between the highly studied human ALDHs and lesser so prokaryotic models.

scholarly journals Functional expression, quantification and cellular localization of the Hxt2 hexose transporter of Saccharomyces cerevisiae tagged with the green fluorescent protein

1999 ◽  
Vol 339 (2) ◽  
pp. 299-307 ◽  
Author(s):  
Arthur L. KRUCKEBERG ◽  
Ling YE ◽  
Jan A. BERDEN ◽  
Karel van DAM
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Green Fluorescent Protein ◽  
Glucose Transport ◽  
Cellular Localization ◽  
Fluorescent Protein ◽  
Hexose Transporter ◽  
High Concentrations ◽  
Green Fluorescent

The Hxt2 glucose transport protein of Saccharomyces cerevisiae was genetically fused at its C-terminus with the green fluorescent protein (GFP). The Hxt2-GFP fusion protein is a functional hexose transporter: it restored growth on glucose to a strain bearing null mutations in the hexose transporter genes GAL2 and HXT1 to HXT7. Furthermore, its glucose transport activity in this null strain was not markedly different from that of the wild-type Hxt2 protein. We calculated from the fluorescence level and transport kinetics that induced cells had 1.4×105 Hxt2-GFP molecules per cell, and that the catalytic-centre activity of the Hxt2-GFP molecule in vivo is 53 s-1 at 30 °C. Expression of Hxt2-GFP was induced by growth at low concentrations of glucose. Under inducing conditions the Hxt2-GFP fluorescence was localized to the plasma membrane. In a strain impaired in the fusion of secretory vesicles with the plasma membrane, the fluorescence accumulated in the cytoplasm. When induced cells were treated with high concentrations of glucose, the fluorescence was redistributed to the vacuole within 4 h. When endocytosis was genetically blocked, the fluorescence remained in the plasma membrane after treatment with high concentrations of glucose.

Mouse models to study von Willebrand factor structure-function relationships in vivo

2009 ◽  
Vol 29 (01) ◽  
pp. 17-20 ◽  
Author(s):  
I. Marx ◽  
I. Badirou ◽  
R. Pendu ◽  
O. Christophe ◽  
C. V. Denis
Keyword(s):  
Structure Function ◽  
Transient Expression ◽  
Von Willebrand Factor ◽  
Large Size ◽  
Mouse Hepatocytes ◽  
Function Relationship ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) structure-function relationship has been studied only through in vitro approaches. The VWF-deficient mouse model has been extremely useful to examine the in vivo function of VWF but does not allow a more subtle analysis of the relative importance of its different domains. However, considering the large size of VWF and its capacity to interact with various ligands in order to support platelet adhesion and aggregation, the necessity to evaluate independently these interactions appeared increasingly crucial. A recently developed technique, known as hydrodynamic injection, which allows transient expression of a transgene by mouse hepatocytes, proved very useful in this regard. Indeed, transient expression of various VWF mutants in VWF-deficient mice contributed to improve our knowledge about the role of VWF interaction with subendothelial collagens and with platelets receptors in VWF roles in haemostasis and thrombosis. These findings can provide new leads in the development of anti-thrombotic therapies.

scholarly journals CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion

2021 ◽  
Vol 10 (10) ◽  
pp. 2144
Author(s):  
Milosz Pietrus ◽  
Kazimierz Pitynski ◽  
Marcin Waligora ◽  
Katarzyna Milian-Ciesielska ◽  
Monika Bialon ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Plasma Membrane ◽  
Tumor Progression ◽  
Endometrial Carcinoma ◽  
Molecular Level ◽  
Risk Group ◽  
High Risk Group ◽  
Cd133 Expression ◽  
Transmembrane Glycoprotein ◽  
The Impact

Background: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1–3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

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