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Signaling Systems in Membrane-Associated Proteins

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 6427

Special Issue Editor


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Guest Editor
Worcester Polytechnic Institute, Worcester, MA, USA
Interests: cell behavior; calcium signals; membrane-associated proteins; membrane properties; G protein signaling
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Special Issue Information

Dear Colleagues,

Biological membranes regulate communication between the external environment and internal compartments. Aside from serving as a barrier, the structure and content of the membrane itself plays a critical role in generating and propagating cellular signals. This issue examines the series of events that occur when extracellular information is received by plasma membrane and how this information generates various cascades of association/dissociation reactions between signaling molecules that lead to specific intracellular events. Changes in these protein interactions, along with concurrent intracellular signals, allow cells to proliferate, divide, migrate, and/or undergo morphological changes. The articles in this issue focus on signals occurring on the plasma and internal membranes that include enzymes that generate soluble second messengers, such as inositol phosphates, cAMP and Ca2+, as well as insoluble second messengers, such as diacylglycerol and phosphatidylinositide 4,5 bisphosphate. Articles will range from the interfacial association between proteins and the membrane surface that drive enzyme reaction dynamics to how cell membranes promote associations between peripheral proteins. Generation and enhancement of lipid signals and discussion of the properties specific to lipid modifying enzymes will be included. Importantly, the ability of these enzymes to communicate with associated signaling networks to drive cell function under normal and transformed conditions will be highlighted.

Prof. Dr. Suzanne Scarlata
Guest Editor

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Keywords

  • lipid membranes
  • lipid-modifying enzymes
  • membrane organization
  • interfacial activation
  • signaling complexes

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Published Papers (2 papers)

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Research

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19 pages, 3718 KiB  
Article
Simple Does Not Mean Trivial: Behavior of Phosphatidic Acid in Lipid Mono- and Bilayers
by Dominik Drabik and Aleksander Czogalla
Int. J. Mol. Sci. 2021, 22(21), 11523; https://doi.org/10.3390/ijms222111523 - 26 Oct 2021
Cited by 5 | Viewed by 2354
Abstract
Phosphatidic acid (PA) is one of the simplest membrane phospholipids, yet it plays a crucial role in various biologically relevant processes that take place in cells. Since PA generation may be triggered by a variety of factors, very often of antagonistic character, the [...] Read more.
Phosphatidic acid (PA) is one of the simplest membrane phospholipids, yet it plays a crucial role in various biologically relevant processes that take place in cells. Since PA generation may be triggered by a variety of factors, very often of antagonistic character, the specific nature of physiological responses driven by PA is not clear. In order to shed more light on these issues, we carried out a systematic characterization of membranes containing one of the three biologically significant PA molecular species. The effect of these molecules on the properties of membranes composed of phosphatidylcholine and/or cholesterol was assessed in a multidisciplinary approach, including molecular dynamic simulations, flicker noise spectroscopy, and Langmuir monolayer isotherms. The first enables the determination of various macroscopic and microscopic parameters such as lateral diffusion, membrane thickness, and defect analysis. The obtained data revealed a strong interaction between unsaturated PA species and phosphatidylcholine. On the other hand, the behavior of saturated PA was greatly influenced by cholesterol. Additionally, a strong effect on mechanical properties was observed in the case of three-component systems, which could not be explained by the simple extrapolation of parameters of the corresponding two-component systems. Our data show that various PA species are not equivalent in terms of their influence on lipid mono- and bilayers and that membrane composition/properties, particularly those related to the presence of cholesterol, may strongly modulate PA behavior. Full article
(This article belongs to the Special Issue Signaling Systems in Membrane-Associated Proteins)
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11 pages, 906 KiB  
Review
The Role of TRPM2 in Endothelial Function and Dysfunction
by Wioletta Zielińska, Jan Zabrzyński, Maciej Gagat and Alina Grzanka
Int. J. Mol. Sci. 2021, 22(14), 7635; https://doi.org/10.3390/ijms22147635 - 16 Jul 2021
Cited by 14 | Viewed by 3586
Abstract
The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to [...] Read more.
The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases. Full article
(This article belongs to the Special Issue Signaling Systems in Membrane-Associated Proteins)
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