scholarly journals Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]

2016 ◽  
Vol 473 (12) ◽  
pp. 1681-1692 ◽  
Author(s):  
Sourav Kolay ◽  
Urbashi Basu ◽  
Padinjat Raghu
Keyword(s):  
Plasma Membrane ◽  
Eukaryotic Cells ◽  
Head Group ◽  
Molecular Processes ◽  
Lipid Kinase ◽  
Multiple Functions ◽  
Lipid Species ◽  
Subcellular Processes ◽  
Invariant Functional ◽  
Standing Question

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes.

scholarly journals Phosphatidylinositol 4,5-bisphosphate is regenerated by speeding of the PI 4-kinase pathway during long PLC activation

2020 ◽  
Vol 152 (12) ◽  
Author(s):  
Jongyun Myeong ◽  
Lizbeth de la Cruz ◽  
Seung-Ryoung Jung ◽  
Jun-Hee Yeon ◽  
Byung-Chang Suh ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Lipid Kinase ◽  
Agonist Action ◽  
Lipid Species ◽  
Phosphoinositide Cycle ◽  
M1 Muscarinic ◽  
Phosphatidylinositol 4 ◽  
Cellular Compartments ◽  
Regulatory Controls

The dynamic metabolism of membrane phosphoinositide lipids involves several cellular compartments including the ER, Golgi, and plasma membrane. There are cycles of phosphorylation and dephosphorylation and of synthesis, transfer, and breakdown. The simplified phosphoinositide cycle comprises synthesis of phosphatidylinositol in the ER, transport, and phosphorylation in the Golgi and plasma membranes to generate phosphatidylinositol 4,5-bisphosphate, followed by receptor-stimulated hydrolysis in the plasma membrane and return of the components to the ER for reassembly. Using probes for specific lipid species, we have followed and analyzed the kinetics of several of these events during stimulation of M1 muscarinic receptors coupled to the G-protein Gq. We show that during long continued agonist action, polyphosphorylated inositol lipids are initially depleted but then regenerate while agonist is still present. Experiments and kinetic modeling reveal that the regeneration results from gradual but massive up-regulation of PI 4-kinase pathways rather than from desensitization of receptors. Golgi pools of phosphatidylinositol 4-phosphate and the lipid kinase PI4KIIIα (PI4KA) contribute to this homeostatic regeneration. This powerful acceleration, which may be at the level of enzyme activity or of precursor and product delivery, reveals strong regulatory controls in the phosphoinositide cycle.

scholarly journals Molecular architecture of the endocytic TPLATE complex

2021 ◽  
Vol 7 (9) ◽  
pp. eabe7999
Author(s):  
Klaas Yperman ◽  
Jie Wang ◽  
Dominique Eeckhout ◽  
Joanna Winkler ◽  
Lam Dai Vu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Structural Approach ◽  
Eukaryotic Cells ◽  
Molecular Architecture ◽  
Membrane Proteome ◽  
Complex Assembly ◽  
Membrane Interaction ◽  
Structural Insight ◽  
Fresh Insight ◽  
Insight Into

Eukaryotic cells rely on endocytosis to regulate their plasma membrane proteome and lipidome. Most eukaryotic groups, except fungi and animals, have retained the evolutionary ancient TSET complex as an endocytic regulator. Unlike other coatomer complexes, structural insight into TSET is lacking. Here, we reveal the molecular architecture of plant TSET [TPLATE complex (TPC)] using an integrative structural approach. We identify crucial roles for specific TSET subunits in complex assembly and membrane interaction. Our data therefore generate fresh insight into the differences between the hexameric TSET in Dictyostelium and the octameric TPC in plants. Structural elucidation of this ancient adaptor complex represents the missing piece in the coatomer puzzle and vastly advances our functional as well as evolutionary insight into the process of endocytosis.

EGF-and NGF-stimulated translocation of cytohesin-1 to the plasma membrane of PC12 cells requires PI 3-kinase activation and a functional cytohesin-1 PH domain

1999 ◽  
Vol 112 (12) ◽  
pp. 1957-1965 ◽  
Author(s):  
K. Venkateswarlu ◽  
F. Gunn-Moore ◽  
J.M. Tavare ◽  
P.J. Cullen
Keyword(s):  
Plasma Membrane ◽  
Pc12 Cells ◽  
Laser Scanning ◽  
Time Course ◽  
Fluorescent Protein ◽  
Dominant Negative ◽  
Head Group ◽  
Nucleotide Exchange ◽  
Ph Domain

ADP-ribosylation factors (ARFs) are small GTP-binding proteins that function as regulators of eukaryotic vesicle trafficking. Cytohesin-1 is a member of a family of ARF guanine nucleotide-exchange factors that contain a C-terminal pleckstrin homology (PH) domain which has been proposed to bind the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). Here we demonstrate that in vitro, recombinant cytohesin-1 binds, via its PH domain, the inositol head group of PIP3, inositol 1,3,4, 5-tetrakisphosphate (IP4), with an affinity greater than 200-fold higher than the inositol head group of either phosphatidylinositol 4, 5-bisphosphate or phosphatidylinositol 3,4-bisphosphate. Moreover, addition of glycerol or diacetylglycerol to the 1-phosphate of IP4 does not alter the ability to interact with cytohesin-1, data which is entirely consistent with cytohesin-1 functioning as a putative PIP3 receptor. To address whether cytohesin-1 binds PIP3 in vivo, we have expressed a chimera of green fluorescent protein (GFP) fused to the N terminus of cytohesin-1 in PC12 cells. Using laser scanning confocal microscopy we demonstrate that either EGF- or NGF-stimulation of transiently transfected PC12 cells results in a rapid translocation of GFP-cytohesin-1 from the cytosol to the plasma membrane. This translocation is dependent on the cytohesin-1 PH domain and occurs with a time course that parallels the rate of plasma membrane PIP3 production. Furthermore, the translocation requires the ability of either agonist to activate PI 3-kinase, since it is inhibited by wortmannin (100 nM), LY294002 (50 microM) and by coexpression with a dominant negative p85. This data therefore suggests that in vivo cytohesin-1 can interact with PIP3 via its PH domain.

Intracellular signalling

2020 ◽  
pp. 256-265
Author(s):  
R. Andres Floto
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Intracellular Signalling ◽  
Signalling Pathways ◽  
Molecular Processes ◽  
Surface Receptors ◽  
Intracellular Signalling Pathways ◽  
Transmission Of Information ◽  
Effective Transmission

This chapter outlines the general principles of intracellular signalling. Focusing on cell surface receptors, the requirements for effective transmission of information across the plasma membrane are outlined. The principal mechanisms utilized in mammalian signal transduction are described. For each, the pathological consequences of aberrant signalling and means by which pathways can be pharmacologically targeted are described in molecular terms. Intracellular signalling pathways permit the transmission and integration of information within cells. Mammalian receptor signalling relies on only a small number of distinct molecular processes which interact to determine cellular responses. Rapid advances in our knowledge of the mechanisms of intracellular signalling has greatly increased understanding of how cells function physiologically, how they malfunction pathologically, and how their behaviour might be manipulated therapeutically.

Hemolytic Activity of Aminoethyl-dodecanoates

1998 ◽  
Vol 53 (1-2) ◽  
pp. 101-106 ◽  
Author(s):  
H. Kleszczyńska ◽  
J. Łuczyński ◽  
S. Witek ◽  
S. Przestalski
Keyword(s):  
Plasma Membrane ◽  
Membrane Fluidity ◽  
Erythrocyte Membrane ◽  
Hemolytic Activity ◽  
Protonated Form ◽  
Maximum Activity ◽  
Head Group ◽  
Dodecanoic Acid ◽  
Polar Head Group ◽  
Erythrocyte Membrane Fluidity

Abstract The effect of new lysosomotropic compounds on red blood cell hemolysis and erythrocyte membrane fluidity has been investigated. In earlier studies it was shown that the compounds inhibit the growth of yeast and plasma membrane H+-ATPase activity. The study was per­ formed with eight aminoethyl esters of lauric acid variously substituted at nitrogen atom. Esters of dodecanoic acid were chosen for study because at that chain length dimethylaminoethyl esters showed maximum activity. The hemolytic activity of the substances studied exhib­its diversified activity in their interaction with the erythrocyte membrane: they differ in hemolytic activity and affect membrane fluidity differently. Erythrocyte membrane fluidity changes under the effect of those compounds which possess highest hemolytic activity. The hemolytic activity of the aminoesters investigated was found to follow a sequence that de­pended on basicity (i.e. ability of the protonated form formation) of the compound and its polar head group size. The most active are the compounds that possess not more than four carbon atoms substituted at nitrogen and highest pKa value.

scholarly journals Criticality of plasma membrane lipids reflects activation state of macrophage cells

2020 ◽  
Vol 17 (163) ◽  
pp. 20190803 ◽  
Author(s):  
Eugenia Cammarota ◽  
Chiara Soriani ◽  
Raphaelle Taub ◽  
Fiona Morgan ◽  
Jiro Sakai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Critical Point ◽  
Membrane Lipids ◽  
Membrane Receptors ◽  
Interleukin 4 ◽  
Critical Conditions ◽  
Membrane Composition ◽  
Macrophage Cells ◽  
Lipid Species ◽  
Anti Inflammatory

Signalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamic point. Macrophage cells are a key component of the innate immune system, are responsive to infections and regulate the local state of inflammation. We investigate changes in the plasma membrane’s proximity to the critical point as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (interferon γ , Kdo 2-Lipid A, lipopolysaccharide) perturbations induce an increase in the transition temperature of giant plasma membrane vesicles; anti-inflammatory interleukin 4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.

scholarly journals The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications

1995 ◽  
Vol 312 (2) ◽  
pp. 479-484 ◽  
Author(s):  
E A C Wiemer ◽  
P A M Michels ◽  
F R Opperdoes
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Trypanosoma Brucei ◽  
Physiological State ◽  
Bloodstream Form ◽  
Eukaryotic Cells ◽  
Monocarboxylate Transporters ◽  
Facilitated Diffusion ◽  
Selective Inhibitors

The pyruvate produced by glycolysis in the bloodstream form of the trypanosome is excreted into the host bloodstream by a facilitated diffusion carrier. The sensitivity of pyruvate transport for alpha-cyano-4-hydroxycinnamate and the compound UK5099 [alpha-cyano-beta-(1-phenylindol-3-yl)acrylate], which are known to be selective inhibitors of pyruvate (monocarboxylate) transporters present in mitochondria and the plasma membrane of eukaryotic cells, was examined. The trypanosomal pyruvate carrier was found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (Ki = 17 mM) but could be completely blocked by UK5099 (Ki = 49 microM). Inhibition of pyruvate transport resulted in the retention, and concomitant accumulation, of pyruvate within the trypanosomes, causing acidification of the cytosol and osmotic destabilization of the cells. Our results indicate that this physiological state has serious metabolic consequences and ultimately leads to cell death; thereby identifying the pyruvate carrier as a possible target for chemotherapeutic intervention.

scholarly journals Internalization of Phospholipids from the Plasma Membrane of Human Osteoblasts Depends on the Lipid Head Group

1999 ◽  
Vol 14 (5) ◽  
pp. 690-699 ◽  
Author(s):  
Jeanette Libera ◽  
Thomas Pomorski ◽  
Oliviera Josimović-Alasević ◽  
Karl-Gerd Fritsch ◽  
Andreas Herrmann
Keyword(s):  
Plasma Membrane ◽  
Head Group ◽  
Human Osteoblasts ◽  
Lipid Head Group

Lipid order and molecular assemblies in the plasma membrane of eukaryotic cells

2009 ◽  
Vol 37 (5) ◽  
pp. 1056-1060 ◽  
Author(s):  
Marek Cebecauer ◽  
Dylan M. Owen ◽  
Anna Markiewicz ◽  
Anthony I. Magee
Keyword(s):  
Plasma Membrane ◽  
Physical Properties ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Eukaryotic Cells ◽  
Dynamic Nature ◽  
Membrane Components ◽  
Technological Improvements

Multimolecular assemblies on the plasma membrane exhibit dynamic nature and are often generated during the activation of eukaryotic cells. The role of lipids and their physical properties in helping to control the existence of these structures is discussed. Technological improvements for live cell imaging of membrane components are also reviewed.

scholarly journals Monoclonal antibodies as probes of epithelial membrane polarization.

1985 ◽  
Vol 101 (6) ◽  
pp. 2173-2180 ◽  
Author(s):  
R J Turner ◽  
J Thompson ◽  
S Sariban-Sohraby ◽  
J S Handler
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Membrane ◽  
Membrane Lipids ◽  
Apical Plasma Membrane ◽  
Epithelial Cell Line ◽  
Lipid Species ◽  
Antigen Complex ◽  
Kidney Epithelial Cell ◽  
Kidney Epithelial Cell Line ◽  
Lipid Antigen

Monoclonal antibodies directed against antigens in the apical plasma membrane of the toad kidney epithelial cell line A6 were produced to probe the phenomena that underlie the genesis and maintenance of epithelial polarity. Two of these antibodies, 17D7 and 18C3, were selected for detailed study here. 17D7 is directed against a 23-kD peptide found on both the apical and basolateral surfaces of the A6 epithelium whereas 18C3 recognizes a lipid localized to the apical membrane only. This novel observation of an apically localized epithelial lipid species indicates the existence of a specific sorting and insertion process for this, and perhaps other, epithelial plasma membrane lipids. The antibody-antigen complexes formed by both these monoclonal antibodies are rapidly internalized by the A6 cells, but only the 18C3-antigen complex is recycled to the plasma membrane. In contrast to the apical localization of the free antigen, however, the 18C3-antigen complex is recycled to both the apical and basolateral surface of the epithelium, which indicates that monoclonal antibody binding interferes in some way with the normal sorting process for this apical lipid antigen.

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