scholarly journals Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin assembly via ADP release, ATP synthesis and P2X7R activation

2009 ◽  
Vol 122 (4) ◽  
pp. 505-512 ◽  
Author(s):  
M. P. Kuehnel ◽  
M. Reiss ◽  
P. K. Anand ◽  
I. Treede ◽  
D. Holzer ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Atp Synthesis ◽  
Actin Assembly ◽  
Sphingosine 1 Phosphate ◽  
Adp Release ◽  
P2x7r Activation

scholarly journals Sphingosine 1-phosphate in inflammation

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Lijuan Li ◽  
Lixia An ◽  
Lifang Li ◽  
Yongjuan Zhao
Keyword(s):  
Plasma Membrane ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Cell Types ◽  
In Vivo Models ◽  
Integral Role ◽  
Sphingosine 1 Phosphate ◽  
And Migration

Sphingolipids are formed via the metabolism of sphingomyelin, aconstituent of the plasma membrane, or by denovosynthesis. Enzymatic pathways result in the formation of several different lipid mediators, which are known to have important roles in many cellular processes, including proliferation, apoptosis and migration. Several studies now suggest that these sphingolipid mediators, including ceramide, ceramide 1-phosphate and sphingosine 1-phosphate (S1P), are likely to have an integral role in in?ammation. This can involve, for example, activation of pro-in?ammatory transcription factors in different cell types and induction of cyclooxygenase-2, leading to production of pro-in?ammatory prostaglandins. The mode of action of each sphingolipid is different. Increased ceramide production leads to the formation of ceramide-rich areas of the membrane, which may assemble signalling complexes, whereas S1P acts via high-af?nity G-protein-coupled S1P receptors on the plasma membrane. Recent studies have demonstrated that in vitro effects of sphingolipids on in?ammation can translate into in vivo models. This review will highlight the areas of research where sphingolipids are involved in in?ammation and the mechanisms of action of each mediator. In addition, the therapeutic potential of drugs that alter sphingolipid actions will be examined with reference to disease states, such as asthma and in?ammatory bowel disease, which involve important in?ammatory components. A signi?cant body of research now indicates that sphingolipids are intimately involved in the in?ammatory process and recent studies have demonstrated that these lipids, together with associated enzymes and receptors, can provide effective drug targets for the treatment of pathological in?ammation.

Na+-dependent phosphate transporters in the murine osteoclast: cellular distribution and protein interactions

2003 ◽  
Vol 284 (6) ◽  
pp. C1633-C1644 ◽  
Author(s):  
Mohammed A. Khadeer ◽  
Zhihui Tang ◽  
Harriet S. Tenenhouse ◽  
Maribeth V. Eiden ◽  
Heini Murer ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Bone Resorption ◽  
Protein Interactions ◽  
Cellular Localization ◽  
Fluorescent Protein ◽  
Basolateral Membrane ◽  
Atp Synthesis ◽  
Cellular Distribution ◽  
Green Fluorescent ◽  
Carboxy Terminal

We previously demonstrated that inhibition of Na-dependent phosphate (Pi) transport in osteoclasts led to reduced ATP levels and diminished bone resorption. These findings suggested that Na/Picotransporters in the osteoclast plasma membrane provide Pifor ATP synthesis and that the osteoclast may utilize part of the Pireleased from bone resorption for this purpose. The present study was undertaken to define the cellular localization of Na/Picotransporters in the mouse osteoclast and to identify the proteins with which they interact. Using glutathione S-transferase (GST) fusion constructs, we demonstrate that the type IIa Na/Picotransporter (Npt2a) in osteoclast lysates interacts with the Na/H exchanger regulatory factor, NHERF-1, a PDZ protein that is essential for the regulation of various membrane transporters. In addition, NHERF-1 in osteoclast lysates interacts with Npt2a in spite of deletion of a putative PDZ-binding domain within the carboxy terminus of Npt2a. In contrast, deletion of the carboxy-terminal TRL amino acid motif of Npt2a significantly reduced its interaction with NHERF-1 in kidney lysates. Studies in osteoclasts transfected with green fluorescent protein-Npt2a constructs indicated that Npt2a colocalizes with NHERF-1 and actin at or near the plasma membrane of the osteoclast and associates with ezrin, a linker protein associated with the actin cytoskeleton, likely via NHERF-1. Furthermore, we demonstrate by RT/PCR of osteoclast RNA and in situ hybridization that the type III Na/Picotransporter, PiT-1, is also expressed in mouse osteoclasts. To examine the cellular distribution of PiT-1, we infected mouse osteoclasts with a retroviral vector encoding PiT-1 fused to an epitope tag. PiT-1 colocalizes with actin and is present on the basolateral membrane of the polarized osteoclast, similar to that previously reported for Npt2a. Taken together, our data suggest that association of Npt2a with NHERF-1, ezrin, and actin, and of PiT-1 with actin, may be responsible for membrane sorting and regulation of these Na/Picotransporters in the osteoclast.

scholarly journals Multiple Myosins Are Required to Coordinate Actin Assembly with Coat Compression during Compensatory Endocytosis

2007 ◽  
Vol 18 (10) ◽  
pp. 4096-4105 ◽  
Author(s):  
Hoi-Ying E. Yu ◽  
William M. Bement
Keyword(s):  
Plasma Membrane ◽  
Egg Activation ◽  
Actin Assembly ◽  
Cortical Granules ◽  
Simultaneous Inhibition

Actin is involved in endocytosis in organisms ranging from yeast to mammals. In activated Xenopus eggs, exocytosing cortical granules (CGs) are surrounded by actin “coats,” which compress the exocytosing compartments, resulting in compensatory endocytosis. Here, we examined the roles of two myosins in actin coat compression. Myosin-2 is recruited to exocytosing CGs late in coat compression. Inhibition of myosin-2 slows coat compression without affecting actin assembly. This differs from phenotype induced by inhibition of actin assembly, where exocytosing CGs are trapped at the plasma membrane (PM) completely. Thus, coat compression is likely driven in part by actin assembly itself, but it requires myosin-2 for efficient completion. In contrast to myosin-2, the long-tailed myosin-1e is recruited to exocytosing CGs immediately after egg activation. Perturbation of myosin-1e results in partial actin coat assembly and induces CG collapse into the PM. Intriguingly, simultaneous inhibition of actin assembly and myosin-1e prevents CG collapse. Together, the results show that myosin-1e and myosin-2 are part of an intricate machinery that coordinates coat compression at exocytosing CGs.

scholarly journals Silencing of Plasma Membrane Ca2+-ATPase Isoforms 2 and 3 Impairs Energy Metabolism in Differentiating PC12 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Tomasz Boczek ◽  
Malwina Lisek ◽  
Bozena Ferenc ◽  
Antoni Kowalski ◽  
Magdalena Wiktorska ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Atp Synthesis ◽  
Mitochondrial Activity ◽  
Excitable Cells ◽  
Close Link ◽  
Atp Level ◽  
Atp Generation

A close link between Ca2+, ATP level, and neurogenesis is apparent; however, the molecular mechanisms of this relationship have not been completely elucidated. Transient elevations of cytosolic Ca2+may boost ATP synthesis, but ATP is also consumed by ion pumps to maintain a low Ca2+in cytosol. In differentiation process plasma membrane Ca2+ATPase (PMCA) is considered as one of the major players for Ca2+homeostasis. From four PMCA isoforms, the fastest PMCA2 and PMCA3 are expressed predominantly in excitable cells. In the present study we assessed whether PMCA isoform composition may affect energy balance in differentiating PC12 cells. We found that PMCA2-downregulated cells showed higher basal O2consumption, lower NAD(P)H level, and increased activity of ETC. These changes associated with higher[Ca2+]cresulted in elevated ATP level. Since PMCA2-reduced cells demonstrated greatest sensitivity to ETC inhibition, we suppose that the main source of energy for PMCA isoforms 1, 3, and 4 was oxidative phosphorylation. Contrary, cells with unchanged PMCA2 expression exhibited prevalence of glycolysis in ATP generation. Our results with PMCA2- or PMCA3-downregulated lines provide an evidence of a novel role of PMCA isoforms in regulation of bioenergetic pathways, and mitochondrial activity and maintenance of ATP level during PC12 cells differentiation.

scholarly journals Selection and stabilization of endocytic sites by Ede1, a yeast functional homologue of human Eps15

2017 ◽  
Vol 28 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Rebecca Lu ◽  
David G. Drubin
Keyword(s):  
Plasma Membrane ◽  
Late Phase ◽  
Coiled Coil ◽  
Actin Assembly ◽  
Rich Region ◽  
The Third ◽  
Early Proteins ◽  
Coiled Coil Region ◽  
Two Stages ◽  
Proline Rich Region

During clathrin-mediated endocytosis (CME), endocytic-site maturation can be divided into two stages corresponding to the arrival of the early and late proteins at the plasma membrane. The early proteins are required to capture cargo and position the late machinery, which includes proteins involved in actin assembly and membrane scission. However, the mechanism by which early-arriving proteins select and stabilize endocytic sites is not known. Ede1, one of the earliest proteins recruited to endocytic sites, facilitates site initiation and stabilization. Deletion of EDE1 results in fewer CME initiations and defects in the timing of vesicle maturation. Here we made truncation mutants of Ede1 to better understand how different domains contribute to its recruitment to CME sites, site selection, and site maturation. We found that the minimal domains required for efficient Ede1 localization at CME sites are the third EH domain, the proline-rich region, and the coiled-coil region. We also found that many strains expressing ede1 truncations could support a normal rate of site initiation but still had defects in site-maturation timing, indicating separation of Ede1 functions. When expressed in yeast, human Eps15 localized to the plasma membrane, where it recruited late-phase CME proteins and supported productive endocytosis, identifying it as an Ede1 functional homologue.

Glutamate-Induced ATP Synthesis: Relationship between Plasma Membrane Na+/Ca2+ Exchanger and Excitatory Amino Acid Transporters in Brain and Heart Cell Models

2013 ◽  
Vol 84 (4) ◽  
pp. 603-614 ◽  
Author(s):  
Simona Magi ◽  
Sara Arcangeli ◽  
Pasqualina Castaldo ◽  
Annamaria Assunta Nasti ◽  
Liberato Berrino ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Synthesis ◽  
Heart Cell ◽  
Amino Acid Transporters ◽  
Cell Models ◽  
Excitatory Amino Acid Transporters

scholarly journals Plasma membrane sphingomyelin hydrolysis increases hippocampal neuron excitability by sphingosine-1-phosphate mediated mechanisms

2010 ◽  
Vol 114 (2) ◽  
pp. 430-439 ◽  
Author(s):  
Eric Norman ◽  
Roy G. Cutler ◽  
Richard Flannery ◽  
Yue Wang ◽  
Mark P. Mattson
Keyword(s):  
Plasma Membrane ◽  
Hippocampal Neuron ◽  
Neuron Excitability ◽  
Sphingosine 1 Phosphate

Role for stress fiber contraction in surface tension development and stretch-activated channel regulation in C2C12 myoblasts

2008 ◽  
Vol 295 (1) ◽  
pp. C160-C172 ◽  
Author(s):  
Francesca Sbrana ◽  
Chiara Sassoli ◽  
Elisabetta Meacci ◽  
Daniele Nosi ◽  
Roberta Squecco ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Myosin Ii ◽  
Cell Stiffness ◽  
C2c12 Myoblasts ◽  
Tension Development ◽  
Force Microscopy ◽  
Atomic Force ◽  
Sphingosine 1 Phosphate ◽  
Membrane Stretching

Membrane-cytoskeleton interaction regulates transmembrane currents through stretch-activated channels (SACs); however, the mechanisms involved have not been tested in living cells. We combined atomic force microscopy, confocal immunofluorescence, and patch-clamp analysis to show that stress fibers (SFs) in C2C12 myoblasts behave as cables that, tensed by myosin II motor, activate SACs by modifying the topography and the viscoelastic (Young's modulus and hysteresis) and electrical passive (membrane capacitance, Cm) properties of the cell surface. Stimulation with sphingosine 1-phosphate to elicit SF formation, the inhibition of Rho-dependent SF formation by Y-27632 and of myosin II-driven SF contraction by blebbistatin, showed that not SF polymerization alone but the generation of tensional forces by SF contraction were involved in the stiffness response of the cell surface. Notably, this event was associated with a significant reduction in the amplitude of the cytoskeleton-mediated corrugations in the cell surface topography, suggesting a contribution of SF contraction to plasma membrane stretching. Moreover, Cm, used as an index of cell surface area, showed a linear inverse relationship with cell stiffness, indicating participation of the actin cytoskeleton in plasma membrane remodeling and the ability of SF formation to cause internalization of plasma membrane patches to reduce Cm and increase membrane tension. SF contraction also increased hysteresis. Together, these data provide the first experimental evidence for a crucial role of SF contraction in SAC activation. The related changes in cell viscosity may prevent SAC from abnormal activation.

scholarly journals Phosphorylation of Nephrin induces phase separated domains that move through actomyosin contraction

2019 ◽  
Author(s):  
Soyeon Kim ◽  
Joseph M. Kalappurakkal ◽  
Satyajit Mayor ◽  
Michael K. Rosen
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Cell Periphery ◽  
Actin Assembly ◽  
Regulatory Pathway ◽  
Basal Plasma Membrane ◽  
Basal Plasma ◽  
Multivalent Interactions ◽  
And Control ◽  
Actomyosin Contraction

AbstractThe plasma membrane of eukaryotic cells is organized into lipid and protein microdomains, whose assembly mechanisms and functions are incompletely understood. We demonstrate that proteins in the Nephrin/Nck/N-WASP actin-regulatory pathway cluster into micron-scale domains at the basal plasma membrane upon triggered phosphorylation of transmembrane Nephrin. The domains are persistent but readily exchange components with their surroundings, and their formation is dependent on the number of Nck SH3 domains, suggesting they are phase separated polymers assembled through multivalent interactions among the three proteins. The domains form independent of the actin cytoskeleton, but acto-myosin contractility induces their rapid lateral movement. Nephrin phosphorylation induces larger clusters at the cell periphery, which are associated with extensive actin assembly and dense filopodia. Our studies illustrate how multivalent interactions between proteins at the plasma membrane can produce micron-scale organization of signaling molecules, and how the resulting clusters can both respond to and control the actin cytoskeleton.

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