Abnormalities in Membrane Lipids, Membrane-Associated Proteins, and Signal Transduction in Autism

Autism ◽  
2009 ◽  
pp. 177-206 ◽  
Author(s):  
Ved Chauhan ◽  
Abha Chauhan
Keyword(s):  
Signal Transduction ◽  
Membrane Lipids ◽  
Associated Proteins

Regulation of ecto-5′-nucleotidase activity via Ca2+-dependent, annexin 2-mediated membrane rearrangement?

2006 ◽  
Vol 34 (3) ◽  
pp. 374-376 ◽  
Author(s):  
E.B. Babiychuk ◽  
A. Draeger
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Lipid Rafts ◽  
Binding Proteins ◽  
Extracellular Atp ◽  
Membrane Rafts ◽  
Nucleotidase Activity ◽  
Annexin 2 ◽  
Associated Proteins ◽  
A Cell

The spatial segregation of the plasma membrane plays a prominent role in distinguishing and sorting a large number of signals a cell receives simultaneously. The plasma membrane comprises regions known as lipid rafts, which serve as signal-transduction hubs and platforms for sorting membrane-associated proteins. Ca2+-binding proteins of the annexin family have been ascribed a role in the regulation of raft dynamics. Glycosylphosphatidylinositol-anchored 5′-nucleotidase is an extracellular, raft-associated enzyme responsible for conversion of extracellular ATP into adenosine. Our results point to a regulation of ecto-5′-nucleotidase activity by Ca2+-dependent, annexin-mediated stabilization of membrane rafts.

Endothelial shear stress responses: mechanotransduction, cell stress and adaptation

2017 ◽  
pp. 112-125
Author(s):  
А.А. Московцев ◽  
Д.В. Колесов ◽  
А.Н. Мыльникова ◽  
Д.М. Зайченко ◽  
А.А. Соколовская ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Stress Response ◽  
Stress Responses ◽  
Intracellular Signaling ◽  
Cellular Response ◽  
Membrane Lipids ◽  
Regulatory Elements

Эндотелиальные клетки, выстилающие стенки сосудов, являются одними из важнейших регуляторных элементов кровеносной системы. Непосредственно соприкасаясь с потоком крови, эти механочувствительные клетки способны детектировать свою деформацию через ее тангенциальный компонент (сдвиг) и составляющую, направленную по нормали к поверхности (растяжение). Деформация сдвига является ключевым индуктором комплекса сигнальных путей, опосредуемых тирозинкиназами, интегринами, ионными каналами, вовлекающих также мембранные липиды, гликокаликс и другие клеточные компоненты. На фоне достаточно большого количества данных о сигнальной трансдукции, в литературе меньше внимания уделено клеточной адаптации к сдвиговой деформации и сравнительно мало информации об участии генов стрессового ответа. Гидродинамические условия в определенных зонах сосудистой системы характеризуются значительной неоднородностью, что может приводить к ослаблению обратных связей, необходимых для поддержания гомеостаза в эндотелиальных клетках. Это может способствовать развитию заболеваний, например, таких, как атеросклероз. В обзоре обсуждаются новые аспекты и концепции, связанные с ответами эндотелиоцитов на сдвиговую деформацию и основные методы анализа эффектов сдвиговой деформации in vitro . Цель исследования. Обобщение современных данных о механизмах механочувствительности и механотрансдукции эндотелия. Результаты. В обзоре изложены основные механизмы механочувствительности клеток эндотелия, пути внутриклеточной передачи сигнала, рассмотрено вовлечение механизмов стрессового ответа клеток и адаптации. Обсуждаются эксперименты по изучению молекулярных основ механотрансдукции, в том числе белков и других молекул, вовлеченных в детектирование, передачу сигнала и клеточный ответ на сдвиговую деформацию. Endothelial cells lining the walls of blood vessels are one of the most important regulatory elements of the circulatory system. These mechanosensitive cells are in a direct contact with the flow of blood and able to detect deformation through its tangential component (shear) and the component directed along the normal to the surface (tension). Shear stress is the key inducer of the complex of signaling pathways mediated by tyrosine kinases, integrins, ion channels, involving also membrane lipids, glycocalyx and other cellular components. There are large amount of data on signal transduction in the literature, but less attention is paid to cellular adaptation to shear stress and there is relatively little information on the involvement of stress response genes in that process. Hydrodynamic conditions in certain zones of the vascular system are characterized by considerable heterogeneity, which can lead to weakening of feedbacks necessary for maintaining homeostasis in endothelial cells. This can contribute to the development of diseases such as atherosclerosis. This review presents new aspects and concepts related to the responses of endotheliocytes to shear stress and, in addition, highlights the basic methods of analyzing the effects of shear stress in vitro . Purpose of the study. Generalization of modern data on mechanisms of mechanosensitivity and mechanotransduction of the endothelium. Results. The review outlines the main mechanosensitivity mechanisms of endothelial cells, the pathways of intracellular signaling, the involvement of mechanisms of cellular stress response and adaptation. There are descriptions of experiments in which the molecular basis of mechanotransduction is identified, including the determination of proteins and other molecules involved in detection, signal transduction, and cellular response to shear stress.

scholarly journals Lipid rafts and regulation of the cytoskeleton during T cell activation

2005 ◽  
Vol 360 (1461) ◽  
pp. 1663-1672 ◽  
Author(s):  
Karina F Meiri
Keyword(s):  
T Cell ◽  
Lipid Rafts ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Membrane Lipids ◽  
Actin Dynamics ◽  
Associated Proteins ◽  
Liquid Ordered

The ability of polarized cells to initiate and sustain directional responses to extracellular signals is critically dependent on direct communication between spatially organized signalling modules in the membrane and the underlying cytoskeleton. Pioneering work in T cells has shown that the assembly of signalling modules critically depends on the functional compartmentalization of membrane lipids into ordered microdomains or lipid rafts. The significance of rafts in T cell activation lies not only in their ability to recruit the signalling partners that eventually assemble into a mature immunological synapse but also in their ability to regulate actin dynamics and recruit cytoskeletal associated proteins, thereby achieving the structural polarization underlying stability of the synapse—a critical prerequisite for activation to be sustained. Lipid rafts vary quite considerably in size and visualizing the smallest of them in vivo has been challenging. Nonetheless it is now been shown quite convincingly that a surprisingly large proportion—in the order of 50%—of external membrane lipids (chiefly cholesterol and glycosphingolipids) can be dynamically localized in these liquid ordered rafts. Complementary inner leaflet rafts are less well characterized, but contain phosphoinositides as an important functional component that is crucial for regulating the behaviour of the actin cytoskeleton. This paper provides an overview of the interdependency between signalling and cytoskeletal polarization, and in particular considers how regulation of the cytoskeleton plays a crucial role in the consolidation of rafts and their stabilization into the immunological synapse.

Glutathione protects signal transduction in type II cells under oxidant stress

1994 ◽  
Vol 266 (2) ◽  
pp. L172-L177 ◽  
Author(s):  
L. A. Brown
Keyword(s):  
Signal Transduction ◽  
Membrane Lipids ◽  
Cell Model ◽  
Oxidant Stress ◽  
Gamma Glutamyl Transferase ◽  
Type Ii Cells ◽  
Type Ii ◽  
Oxidant Injury ◽  
Surfactant Secretion ◽  
Glutamyl Transferase

Brief exposure of type II cells to 100 microM t-butyl hydroperoxide (tBOOH) inhibits agonist-induced surfactant secretion and second messenger generation presumably through the oxidation of membrane lipids. Since glutathione (GSH) reduces lipid peroxides and protects type II cells from oxidant injury as determined by crude indicators, then GSH should also protect signal transduction. In the current study, tBOOH inhibited ATP-induced adenosine 3',5'-cyclic monophosphate and inositol trisphosphate generation and surfactant secretion. Stimulation of surfactant secretion by forskolin or phorbol acetate was also inhibited by tBOOH. Pretreatment with GSH (1 mM) blocked the tBOOH inhibition. This protection occurred in the presence of gamma-glutamyl transferase and gamma-glutamylcysteine synthetase inhibitors and suggested GSH was transported as an intact molecule. GSH protection was blocked by gamma-L-glutamyl-L-glutamate, an agent that blocks GSH transport. Protection of surfactant secretion and signal transduction was also provided by the constitutive amino acids but not if GSH synthesis was blocked. In the cultured type II cell model, GSH transport and synthesis protected signal transduction and, subsequently, surfactant secretion against oxidant injury.

scholarly journals Domain architecture of the smooth-muscle plasma membrane: regulation by annexins

2005 ◽  
Vol 387 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Annette DRAEGER ◽  
Susan WRAY ◽  
Eduard B. BABIYCHUK
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Lipids ◽  
Domain Architecture ◽  
Focal Adhesions ◽  
Membrane Lipid ◽  
Dependent Manner ◽  
Detailed Structural Analysis ◽  
Specific Subset ◽  
Associated Proteins

Individual signalling events are processed in distinct, spatially segregated domains of the plasma membrane. In a smooth muscle, the sarcolemma is divided into domains of focal adhesions alternating with caveolae-rich zones, both harbouring a specific subset of membrane-associated proteins. Recently, we have demonstrated that the sarcolemmal lipids are similarly segregated into domains of cholesterol-rich lipid rafts and glycerophospholipid-rich non-raft regions. In the present study, we provide a detailed structural analysis of the relationship between these proteinaceous and lipid domains. We demonstrate that the segregation of plasmalemmal protein constituents is intimately linked to that of the membrane lipids. Our results imply that lipid segregation is critical for the preservation of membrane protein architecture and essential for directional translocation of proteins to the sarcolemma. We show that the membrane lipid segregation is supported by the annexin protein family in a Ca2+-dependent manner. Eukaryotic cells harbour numerous, tissue-specific subsets of annexins. By examining the significance of this variety in a smooth muscle, we demonstrate that four different annexins target membrane sites of distinct lipid composition and that each annexin requires a different [Ca2+] for its translocation to the sarcolemma. Our results suggest that the interactions of annexins with distinct plasma membrane regions promote membrane segregation and, in combination with their individual Ca2+ sensitivity, might allow a spatially confined, graded response to a multitude of extra- or intracellular stimuli.

scholarly journals IκB Kinase (IKK)-Associated Protein 1, a Common Component of the Heterogeneous IKK Complex

1999 ◽  
Vol 19 (2) ◽  
pp. 1526-1538 ◽  
Author(s):  
Frank Mercurio ◽  
Brion W. Murray ◽  
Andrej Shevchenko ◽  
Brydon L. Bennett ◽  
David B. Young ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Binding Domain ◽  
Necrosis Factor Alpha ◽  
Common Component ◽  
Signal Transduction Cascade ◽  
Iκb Kinase ◽  
Associated Proteins

ABSTRACT Activation of the transcription factor NF-κB is controlled by the sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit, IκB. We recently purified a large multiprotein complex, the IκB kinase (IKK) signalsome, which contains two regulated IκB kinases, IKK1 and IKK2, that can each phosphorylate IκBα and IκBβ. The IKK signalsome contains several additional proteins presumably required for the regulation of the NFκB signal transduction cascade in vivo. In this report, we demonstrate reconstitution of IκB kinase activity in vitro by using purified recombinant IKK1 and IKK2. Recombinant IKK1 or IKK2 forms homo- or heterodimers, suggesting the possibility that similar IKK complexes exist in vivo. Indeed, in HeLa cells we identified two distinct IKK complexes, one containing IKK1-IKK2 heterodimers and the other containing IKK2 homodimers, which display differing levels of activation following tumor necrosis factor alpha stimulation. To better elucidate the nature of the IKK signalsome, we set out to identify IKK-associated proteins. To this end, we purified and cloned a novel component common to both complexes, named IKK-associated protein 1 (IKKAP1). In vitro, IKKAP1 associated specifically with IKK2 but not IKK1. Functional analyses revealed that binding to IKK2 requires sequences contained within the N-terminal domain of IKKAP1. Mutant versions of IKKAP1, which either lack the N-terminal IKK2-binding domain or contain only the IKK2-binding domain, disrupt the NF-κB signal transduction pathway. IKKAP1 therefore appears to mediate an essential step of the NF-κB signal transduction cascade. Heterogeneity of IKK complexes in vivo may provide a mechanism for differential regulation of NF-κB activation.

scholarly journals Phosphoinositides: Navigation through the endosomal maze

2009 ◽  
Vol 31 (5) ◽  
pp. 20-25 ◽  
Author(s):  
Anna C. Rutherford ◽  
Peter J. Cullen
Keyword(s):  
Signal Transduction ◽  
Membrane Lipids ◽  
Signal Transduction Pathways ◽  
Intracellular Membranes

For many years, the phosphoinositide (PI) family of membrane lipids was studied because of its importance as intermediates in signal transduction pathways. Over the last decade, it has become increasingly clear that, in addition to these signalling functions, PIs are one of the key regulators governing the identity of intracellular membranes and the flux of membrane through the cell.

Sign in / Sign up

Export Citation Format

Share Document