scholarly journals The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1065
Author(s):  
Armando Rubio-Ramos ◽  
Leticia Labat-de-Hoz ◽  
Isabel Correas ◽  
Miguel A. Alonso

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

Author(s):  
W.T. Gunning ◽  
M.R. Marino ◽  
M.S. Babcock ◽  
G.D. Stoner

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.


2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Nikolaos G. Frangogiannis

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β–driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.


2009 ◽  
Vol 83 (8) ◽  
pp. 3816-3825 ◽  
Author(s):  
Mari I. Jonsson ◽  
Annasara E. Lenman ◽  
Lars Frängsmyr ◽  
Cecilia Nyberg ◽  
Mohamed Abdullahi ◽  
...  

ABSTRACT Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.


2000 ◽  
Vol 278 (2) ◽  
pp. F192-F201 ◽  
Author(s):  
Dennis Brown

Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
O. Escribano ◽  
N. Beneit ◽  
C. Rubio-Longás ◽  
A. R. López-Pastor ◽  
A. Gómez-Hernández

The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and IRB. The differential physiological and pathological role of both isoforms is not completely known, and it is determinant the different binding affinity for insulin-like growth factor. IRB is more abundant in adult tissues and it exerts mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal and prenatal period and exerts mitogenic actions. However, the change in the expression profile of both IR isoforms and its dysregulation are associated with the development of different pathologies, such as cancer, insulin resistance, diabetes, obesity, and atherosclerosis. In some of them, there is a significant increase of IRA/IRB ratio conferring a proliferative and migratory advantage to different cell types and favouring IGF-II actions with a sustained detriment in the metabolic effects of insulin. This review discussed specifically the role of IR isoforms as well as IGF-IR in diabetes and its associated complications as obesity and atherosclerosis. Future research with new IR modulators might be considered as possible targets to improve the treatment of diabetes and its associated complications.


1998 ◽  
Vol 46 (5) ◽  
pp. 613-626 ◽  
Author(s):  
Phyllis M. Novikoff ◽  
Ana Yam

Microscopic analysis in combination with cytochemistry and immunocytochemistry has revealed the presence of four cell types not previously described in the portal area and parenchyma of the liver from an experimental rodent hepatocarcinogenic rat model. Within the intrahepatic bile ductules, which proliferate after administration of chemical carcinogens and partial hepatectomy, small, undifferentiated nonpolarized, nonepithelial cells with a blast-like phenotype and polarized epithelial cells different from the polarized epithelial cells that typically line the walls of the bile ductules were found. In the connective tissue stroma surrounding the bile ductules, nonpolarized epithelial cells with hepatocyte phenotype were found. In the parenchyma, subpopulations of bile ductule epithelial cells that established ATPase-positive bile canalicular structures, including the formation of desmosomes and tight junctions, with parenchymal hepatocytes within the hepatic lobule were found. These observations raise the following questions in this model. Are there undifferentiated progenitor cells with stem cell-like properties within bile ductules? What are the interrelations of the newly described cell types with each other, with parenchymal hepatocytes, with preneoplastic nodules, and with hepatomas? Do the heterogeneous cell types within the bile ductules, in the surrounding connective tissue, and within the hepatic cords represent intermediate stages of single or multiple cell lineage pathways leading to hepatocyte differentiation, liver regeneration, and/or preneoplastic nodule formation?


2016 ◽  
Vol 113 (27) ◽  
pp. 7470-7474 ◽  
Author(s):  
Cyrus K. Foroughi ◽  
Samuel S. Monfort ◽  
Martin Paczynski ◽  
Patrick E. McKnight ◽  
P. M. Greenwood

Although a large body of research shows that general cognitive ability is heritable and stable in young adults, there is recent evidence that fluid intelligence can be heightened with cognitive training. Many researchers, however, have questioned the methodology of the cognitive-training studies reporting improvements in fluid intelligence: specifically, the role of placebo effects. We designed a procedure to intentionally induce a placebo effect via overt recruitment in an effort to evaluate the role of placebo effects in fluid intelligence gains from cognitive training. Individuals who self-selected into the placebo group by responding to a suggestive flyer showed improvements after a single, 1-h session of cognitive training that equates to a 5- to 10-point increase on a standard IQ test. Controls responding to a nonsuggestive flyer showed no improvement. These findings provide an alternative explanation for effects observed in the cognitive-training literature and the brain-training industry, revealing the need to account for confounds in future research.


2021 ◽  
Vol 11 ◽  
Author(s):  
P. Boknik ◽  
J. Eskandar ◽  
B. Hofmann ◽  
N. Zimmermann ◽  
J. Neumann ◽  
...  

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.


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