The membrane environment of cadherin adhesion receptors: a working hypothesis

2019 ◽  
Vol 47 (4) ◽  
pp. 985-995 ◽  
Author(s):  
Jessica L. Teo ◽  
Robert G. Parton ◽  
Alpha S. Yap
Keyword(s):  
Cell Biology ◽  
Membrane Lipid ◽  
Integral Membrane Proteins ◽  
Mechanical Tension ◽  
Adhesion Receptors ◽  
Tissue Integrity ◽  
Molecular Composites ◽  
Mediate Cell ◽  
Lipid Environment ◽  
Membrane Spanning

Abstract Classical cadherin cell adhesion receptors are integral membrane proteins that mediate cell–cell interactions, tissue integrity and morphogenesis. Cadherins are best understood to function as membrane-spanning molecular composites that couple adhesion to the cytoskeleton. On the other hand, the membrane lipid environment of the cadherins is an under-investigated aspect of their cell biology. In this review, we discuss two lines of research that show how the membrane can directly or indirectly contribute to cadherin function. Firstly, we consider how modification of its local lipid environment can potentially influence cadherin signalling, adhesion and dynamics, focusing on a role for phosphoinositide-4,5-bisphosphate. Secondly, we discuss how caveolae may indirectly regulate cadherins by modifying either the lipid composition and/or mechanical tension of the plasma membrane. Thus, we suggest that the membrane is a frontier of cadherin biology that is ripe for re-exploration.

scholarly journals Membrane Lipid Composition of the Moderately Thermophilic Ammonia-Oxidizing Archaeon “Candidatus Nitrosotenuis uzonensis” at Different Growth Temperatures

2019 ◽  
Vol 85 (20) ◽  
Author(s):  
Nicole J. Bale ◽  
Marton Palatinszky ◽  
W. Irene C. Rijpstra ◽  
Craig W. Herbold ◽  
Michael Wagner ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Strong Influence ◽  
Thermal Spring ◽  
Membrane Lipid ◽  
Effect Of Temperature ◽  
Environmental Niche ◽  
Membrane Lipid Composition ◽  
Moderately Thermophilic ◽  
Wide Range ◽  
Membrane Spanning

ABSTRACT “Candidatus Nitrosotenuis uzonensis” is the only cultured moderately thermophilic member of the thaumarchaeotal order Nitrosopumilales (NP) that contains many mesophilic marine strains. We examined its membrane lipid composition at different growth temperatures (37°C, 46°C, and 50°C). Its lipids were all membrane-spanning glycerol dialkyl glycerol tetraethers (GDGTs), with 0 to 4 cyclopentane moieties. Crenarchaeol (cren), the characteristic thaumarchaeotal GDGT, and its isomer (crenʹ) were present in high abundance (30 to 70%). The GDGT polar headgroups were mono-, di-, and trihexoses and hexose/phosphohexose. The ratio of glycolipid to phospholipid GDGTs was highest in the cultures grown at 50°C. With increasing growth temperatures, the relative contributions of cren and crenʹ increased, while those of GDGT-0 to GDGT-4 (including isomers) decreased. TEX86 (tetraether index of tetraethers consisting of 86 carbons)-derived temperatures were much lower than the actual growth temperatures, further demonstrating that TEX86 does not accurately reflect the membrane lipid adaptation of thermophilic Thaumarchaeota. As the temperature increased, specific GDGTs changed relative to their isomers, possibly representing temperature adaption-induced changes in cyclopentane ring stereochemistry. Comparison of a wide range of thaumarchaeotal core lipid compositions revealed that the “Ca. Nitrosotenuis uzonensis” cultures clustered separately from other members of the NP order and the Nitrososphaerales (NS) order. While phylogeny generally seems to have a strong influence on GDGT distribution, our analysis of “Ca. Nitrosotenuis uzonensis” demonstrates that its terrestrial, higher-temperature niche has led to a lipid composition that clearly differentiates it from other NP members and that this difference is mostly driven by its high crenʹ content. IMPORTANCE For Thaumarchaeota, the ratio of their glycerol dialkyl glycerol tetraether (GDGT) lipids depends on growth temperature, a premise that forms the basis of the widely applied TEX86 paleotemperature proxy. A thorough understanding of which GDGTs are produced by which Thaumarchaeota and what the effect of temperature is on their GDGT composition is essential for constraining the TEX86 proxy. “Ca. Nitrosotenuis uzonensis” is a moderately thermophilic thaumarchaeote enriched from a thermal spring, setting it apart in its environmental niche from the other marine mesophilic members of its order. Indeed, we found that the GDGT composition of “Ca. Nitrosotenuis uzonensis” cultures was distinct from those of other members of its order and was more similar to those of other thermophilic, terrestrial Thaumarchaeota. This suggests that while phylogeny has a strong influence on GDGT distribution, the environmental niche that a thaumarchaeote inhabits also shapes its GDGT composition.

Specificity and promiscuity in membrane helix interactions

1994 ◽  
Vol 27 (2) ◽  
pp. 157-218 ◽  
Author(s):  
Mark A. Lemmon ◽  
Donald M. Engelman
Keyword(s):  
Membrane Proteins ◽  
Transmembrane Helix ◽  
Integral Membrane Proteins ◽  
Lipid Packing ◽  
Membrane Protein Folding ◽  
Membrane Spanning ◽  
Α Helix ◽  
Prosthetic Groups ◽  
Packing Effects ◽  
Helix Interactions

The membrane-spanning portions of many integral membrane proteins consist of one or a number of transmembrane α-helices, which are expected to be independently stable on thermodynamic grounds. Side-by-side interactions between these transmembrane α-helices are important in the folding and assembly of such integral membrane proteins and their complexes. In considering the contribution of these helix–helix interactions to membrane protein folding and oligomerization, a distinction between the energetics and specificity should be recognized. A number of contributions to the energetics of transmembrane helix association within the lipid bilayer will be relatively non-specific, including those resulting from charge–charge interactions and lipid–packing effects. Specificity (and part of the energy) in transmembrane α-helix association, however, appears to rely mainly upon a detailed stereochemical fit between sets of dynamically accessible states of particular helices. In some cases, these interactions are mediated in part by prosthetic groups.

PI(4,5)P2 Clustering and Its Impact on Biological Functions

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Yi Wen ◽  
Volker M. Vogt ◽  
Gerald W. Feigenson
Keyword(s):  
Plasma Membrane ◽  
Cell Biology ◽  
Cellular Proteins ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Cellular Functions ◽  
Dynamic Distribution ◽  
Multivalent Cation ◽  
Lipid Environment

Located at the inner leaflet of the plasma membrane, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] comprises only 1–2 mol% of total PM lipids. With its synthesis and turnover both spatially and temporally regulated, PI(4,5)P2 recruits and interacts with hundreds of cellular proteins to support a broad spectrum of cellular functions. Several factors contribute to the versatile and dynamic distribution of PI(4,5)P2 in membranes. Physiological multivalent cations such as Ca2+ and Mg2+ can bridge between PI(4,5)P2 headgroups, forming nanoscopic PI(4,5)P2–cation clusters. The distinct lipid environment surrounding PI(4,5)P2 affects the degree of PI(4,5)P2 clustering. In addition, diverse cellular proteins interacting with PI(4,5)P2 can further regulate PI(4,5)P2 lateral distribution and accessibility. This review summarizes the current understanding of PI(4,5)P2 behavior in both cells and model membranes, with emphasis on both multivalent cation– and protein-induced PI(4,5)P2 clustering. Understanding the nature of spatially separated pools of PI(4,5)P2 is fundamental to cell biology. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Role of Integrin αvβ3 in Vascular Biology

1998 ◽  
Vol 80 (11) ◽  
pp. 726-734 ◽  
Author(s):  
Tatiana Byzova ◽  
Ramin Rabbani ◽  
Stanley D’Souza ◽  
Edward Plow
Keyword(s):  
Cell Biology ◽  
Cell Function ◽  
Thrombus Formation ◽  
Cellular Adhesion ◽  
Vascular Cells ◽  
Functional Responses ◽  
Adhesive Properties ◽  
Adhesion Receptors ◽  
Vascular Cell

IntroductionA defining characteristic of vascular cells is their adhesive status. The predominant cells of the blood vessel, endothelial cells (EC) and smooth muscle cells (SMC), are normally adherent but can be induced to migrate in response to vascular injury and angiogenic stimuli. The circulating blood cells are ordinarily nonadhesive but can rapidly acquire an adhesive phenotype in response to physiologic and pathophysiologic stimuli. As prime examples, platelets become adherent to the subendothelial matrix and to one another during thrombus formation, and leukocytes first adhere to EC and then transmigrate during the inflammatory response. At a molecular level, the adhesive properties of the vascular cells are determined by the adhesion receptors on their cell-surface and the functional state of these receptors. To match the variety of requisite cellular adhesive reactions, the repertoire of adhesion receptors expressed by vascular cells is broad. Multiple representatives of the immunoglobulin-like, the selectin, the cadherin and the integrin families of adhesion receptors are present on and have been implicated in the functions of the vascular cells. The importance of these adhesion receptors in vascular cell function is underscored by the severe pathogenetic consequences of their congenital deficiencies, such as in Glanzmann’s thrombasthenia, LAD (Leucocyte Adhesion deficiency) I and LAD II (1-3).The integrins are the largest and most broadly distributed of the families of cellular adhesion receptors. Of the integrins, αvβ3, originally identified as the vitronectin receptor, is particularly widely distributed. It is expressed at variable density on many types of vascular cells. Obviously, the adhesive properties of a cell are determined by its full repertoire of adhesion receptors. As an example, the adhesion of EC to fibrinogen/fibrin is mediated by no fewer than five receptors. Nevertheless, it is possible to dissect out the contributions of individual adhesion receptors, and αvβ3 has been implicated in many functional responses of vascular cells. This review focusses upon the role of αvβ3 in vascular cell biology. Other contributions of this multifunctional receptor, such as its role in neoplastic growth and invasion and in osteoclast-mediated bone resorption, are beyond the scope of this article and have been reviewed elsewhere (4, 5).

scholarly journals Dynamic modulation of mitochondrial membrane physical properties and ATPase activity by diet lipid

1981 ◽  
Vol 198 (1) ◽  
pp. 167-175 ◽  
Author(s):  
S M Innis ◽  
M T Clandinin
Keyword(s):  
Fatty Acid ◽  
Rapeseed Oil ◽  
Membrane Lipid ◽  
Dietary Lipid ◽  
Soya Bean ◽  
The Body ◽  
Kinetic Properties ◽  
Mitochondrial Atpase ◽  
Lipid Environment

A longitudinal cross-over feeding design was used to investigate the relationship of dietary lipid composition to the membrane lipid environment and activity of mitochondrial ATPase in vivo. Rats were fed a polyunsaturated fatty-acid-rich oil (soya-bean oil) for 12 days, crossed-over to a monounsaturated fatty-acid-rich oil (rapeseed oil) for the next 11 days, then returned to soya-bean oil for 11 more days. Additional rats were fed either soya-bean oil or rapeseed oil throughout. Rats fed rapeseed oil had lower rates of ATPase-catalysed ATP/[32P]Pi exchange than rats fed soya-bean oil. Arrhenius plots showed higher transition temperature (Tt) and activation energy (Ea) for rats fed rapeseed oil. Switching from soya-bean oil to rapeseed oil was dynamically followed by changes in the thermotropic and kinetic properties of the mitochondrial ATPase exchange reaction. Returning to soya-bean oil reversed these changes. The rapid and reversible modulation of Tt caused by a change of the type of fat ingested suggests that membrane physicochemical properties are not under rigid intrinsic control but are continually modified by the profile of exogenously derived fatty acids. The studies suggest that in vivo the activity of mitochondrial ATPase is in part determined by dietary lipid via its influence on the microenvironment of the enzyme. The rapidity and ready reversibility of changes observed for this subcellular-membrane-bound enzyme suggest that dietary fatty-acid balance may be an important determinant of other membrane functions in the body.

scholarly journals Desmoplakin Is Required Early in Development for Assembly of Desmosomes and Cytoskeletal Linkage

1998 ◽  
Vol 143 (7) ◽  
pp. 2009-2022 ◽  
Author(s):  
G. Ian Gallicano ◽  
Panos Kouklis ◽  
Christoph Bauer ◽  
Mei Yin ◽  
Valeri Vasioukhin ◽  
...  
Keyword(s):  
Critical Role ◽  
Early Embryo ◽  
Cell Junctions ◽  
Epithelial Polarity ◽  
Tissue Architecture ◽  
Desmosomal Cadherins ◽  
Tissue Integrity ◽  
Classical Cadherins ◽  
Mediate Cell ◽  
Cell Cell

Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell–cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous −/− mutant embryos proceeded through implantation, but did not survive beyond E6.5. Mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (−/−) embryos, the paucity of desmosomal cell–cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.

scholarly journals Flexible Surface Model Explains Time-Resolved Uv-Visible Studies of Rhodopsin Activation in a Membrane Lipid Environment

2011 ◽  
Vol 100 (3) ◽  
pp. 338a
Author(s):  
James W. Lewis ◽  
Istvan Szundi ◽  
David S. Kliger ◽  
Michael F. Brown
Keyword(s):  
Membrane Lipid ◽  
Surface Model ◽  
Time Resolved ◽  
Flexible Surface ◽  
Uv Visible ◽  
Lipid Environment

Effect of the Membrane Lipid Environment on the Properties of Insulin Receptors

Diabetes ◽  
1981 ◽  
Vol 30 (9) ◽  
pp. 773-780 ◽  
Author(s):  
B. H. Ginsberg ◽  
T. J. Brown ◽  
I. Simon ◽  
A. A. Spector
Keyword(s):  
Insulin Receptors ◽  
Membrane Lipid ◽  
Lipid Environment

scholarly journals Epidermal Growth Factor Receptor Activation Remodels the Plasma Membrane Lipid Environment To Induce Nanocluster Formation

2010 ◽  
Vol 30 (15) ◽  
pp. 3795-3804 ◽  
Author(s):  
Nicholas Ariotti ◽  
Hong Liang ◽  
Yufei Xu ◽  
Yueqiang Zhang ◽  
Yoshiya Yonekubo ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Membrane Lipid ◽  
Dependent Manner ◽  
Epidermal Growth ◽  
Lipid Environment ◽  
Lateral Segregation

ABSTRACT Signal transduction is regulated by the lateral segregation of proteins into nanodomains on the plasma membrane. However, the molecular mechanisms that regulate the lateral segregation of cell surface receptors, such as receptor tyrosine kinases, upon ligand binding are unresolved. Here we used high-resolution spatial mapping to investigate the plasma membrane nanoscale organization of the epidermal growth factor (EGF) receptor (EGFR). Our data demonstrate that in serum-starved cells, the EGFR exists in preformed, cholesterol-dependent, actin-independent nanoclusters. Following stimulation with EGF, the number and size of EGFR nanoclusters increase in a time-dependent manner. Our data show that the formation of EGFR nanoclusters requires receptor tyrosine kinase activity. Critically, we show for the first time that production of phosphatidic acid by phospholipase D2 (PLD2) is essential for ligand-induced EGFR nanocluster formation. In accordance with its crucial role in regulating EGFR nanocluster formation, we demonstrate that modulating PLD2 activity tunes the degree of EGFR nanocluster formation and mitogen-activated protein kinase signal output. Together, these data show that EGFR activation drives the formation of signaling domains by regulating the production of critical second-messenger lipids and modifying the local membrane lipid environment.

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