Spontaneous cellular vibratory motions of osteocytes are regulated by ATP and spectrin network

Bone ◽  
2019 ◽  
Vol 128 ◽  
pp. 112056
Author(s):  
Xin-Tong Wu ◽  
Wen Xiao ◽  
Run-Yu Cao ◽  
Xiao Yang ◽  
Feng Pan ◽  
...  
Keyword(s):  
Spectrin Network

scholarly journals Drosophila development requires spectrin network formation.

1995 ◽  
Vol 128 (1) ◽  
pp. 71-79 ◽  
Author(s):  
H Deng ◽  
J K Lee ◽  
L S Goldstein ◽  
D Branton
Keyword(s):  
Network Formation ◽  
Recombinant Dna ◽  
Point Mutations ◽  
Drosophila Genome ◽  
Dependent Manner ◽  
Null Mutant ◽  
Alpha Spectrin ◽  
Spectrin Network

The head-end associations of spectrin give rise to tetramers and make it possible for the molecule to form networks. We analyzed the head-end associations of Drosophila spectrin in vitro and in vivo. Immunoprecipitation assays using protein fragments synthesized in vitro from recombinant DNA showed that interchain binding at the head end was mediated by segment 0-1 of alpha-spectrin and segment 18 of beta-spectrin. Point mutations equivalent to erythroid spectrin mutations that are responsible for human hemolytic anemias diminished Drosophila spectrin head-end interchain binding in vitro. To test the in vivo consequence of deficient head-end interchain binding, we introduced constructs expressing head-end interchain binding mutant alpha-spectrin into the Drosophila genome and tested for rescue of an alpha-spectrin null mutation. An alpha-spectrin minigene lacking the codons for head-end interchain binding failed to rescue the lethality of the null mutant, whereas a minigene with a point mutation in these codons overcame the lethality of the null mutant in a temperature-dependent manner. The rescued flies were viable and fertile at 25 degrees C, but they became sterile because of defects in oogenesis when shifted to 29 degrees C. At 29 degrees C, egg chamber tissue disruption and cell shape changes were evident, even though the mutant spectrin remained stably associated with cell membranes. Our results show that spectrin's capacity to form a network is a crucial aspect of its function in nonerythroid cells.

scholarly journals The actin-capping protein alpha-adducin is required for T-cell costimulation

2019 ◽  
Author(s):  
Timothy J. Thauland ◽  
Manish J. Butte
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Conditional Knockout ◽  
Capping Protein ◽  
Actin Capping Protein ◽  
Actin Capping ◽  
Spectrin Network

AbstractAlpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using a conditional knockout model, we show that Add1 is necessary for complete activation of CD4+ T cells in response to low levels of antigen but is dispensable for CD8+ T cell activation and response to infection. Surprisingly, costimulatory signals through CD28 were completely abrogated in the absence of Add1. This study is the first to examine the role of actin-capping in T cells, and it reveals a previously unappreciated role for the actin cytoskeleton in regulating costimulation.

scholarly journals Transmembrane Signaling Regulates the Remodeling of the Actin Cytoskeleton:Roles of PKC and Adducin

2021 ◽  
Author(s):  
Bih-Hwa Shieh ◽  
Wesley Sun ◽  
Darwin Ferng
Keyword(s):  
Actin Cytoskeleton ◽  
Null Allele ◽  
Dominant Negative ◽  
Visual Signaling ◽  
Kinase C ◽  
Severe Effect ◽  
Cross Links ◽  
Dominant Negative Activity ◽  
Spectrin Network

Members of the conventional protein kinase C (cPKC) family are activated by both DAG and Ca2+ and have been implicated in the regulation of the actin cytoskeleton. Drosophila contains two cPKCs, Pkc53E (Pkc1) and eye-PKC (Pkc2); mutants missing each PKC lead to retinal degeneration. While eye-PKC is critical for the visual signaling, the role of Pkc53E is not known. We identified a photoreceptor-specific isoform of Pkc53E and show Pkc53E-RNAi negatively impacts the actin cytoskeleton of rhabdomeres. Interestingly, Pkc53E-RNAi enhances the degeneration of norpAP24 photoreceptors, suggesting Pkc53E could be activated independently of NorpA/PLCβ4. We further demonstrate that in norpAP24 photoreceptors Plc21C can be activated by Gq, which is responsible for the activation of Pkc53E. We explored whether Pkc53E regulates adducin in Drosophila photoreceptors. Adducin cross-links the actin cytoskeleton to the spectrin network, which is blunted by PKC phosphorylation. Importantly, we observed that phosphorylation of adducin was greatly reduced in a null allele of pkc53E. Downregulation of hts that encodes Drosophila adducin, exerts a more severe effect than Pkc53E-RNAi to impact the actin cytoskeleton. In contrast, overexpression of a mCherry tagged Add2, one of the three Drosophila adducin isoforms, led to the apical expansion of rhabdomeres with overgrowth of the actin cytoskeleton. This phenotype is likely caused by the dominant-negative activity of the tagged Add2 as it also was observed in α-spectrin-RNAi or β-spectrin-RNAi. Interestingly, downregulation of Pkc53E does not suppress the expansion of rhabdomeres during development, but negatively affects the appearance of rhabdomeres in adult photoreceptors. We conclude that Drosophila adducin has two distinct functions: in pupal photoreceptors, it regulates rhabdomere morphogenesis, which is independent of Pkc53E. In adult photoreceptors, it promotes the maintenance of the actin cytoskeleton, which is regulated by Pkc53E in response to the light-induced activation of the PLCβ activity.

The distribution of spectrin along the membranes of normal and echinocytic human erythrocytes

1978 ◽  
Vol 34 (1) ◽  
pp. 91-101
Author(s):  
E. Ziparo ◽  
A. Lemay ◽  
V.T. Marchesi
Keyword(s):  
Cell Membrane ◽  
Cell Shape ◽  
Human Erythrocytes ◽  
Atp Depletion ◽  
Red Cell ◽  
Significant Extent ◽  
Red Cell Membrane ◽  
Extrusion Mechanism ◽  
The Stability ◽  
Spectrin Network

Spectrin molecules are distributed uniformly throughout the submembranous regions of intact human erythrocytes. Spectrin does not appear to extend into the red blood cell cytoplasm to any significant extent. Thus, it does not form a recognizable internal scaffolding nor does it seem to connect distant segments of the cell membrane. Spectrin retains its submembranous location in the spiny processes of echinocytes produced by ATP depletion. Thus, these processes do not seem to form by a simple extrusion mechanism powered by contraction of the spectrin network. Spectrin seems to be important for the stability of the lipid bilayer of the red cell membrane, and it probably also plays a role in regulating red cell shape. How it performs either function is still unknown.

Influence of the spectrin network on fusion of influenza virus with red blood cells

1995 ◽  
Vol 12 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Torsten Reda ◽  
Robert Blumenthal ◽  
Peter Müller ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Spectrin Network

Two-Component Coarse-Grain Model for Erythrocyte Membrane

2011 ◽  
Author(s):  
George Lykotrafitis ◽  
He Li
Keyword(s):  
Shear Stress ◽  
Lipid Bilayer ◽  
Structural Integrity ◽  
Finite Difference Methods ◽  
Coarse Grained ◽  
Erythrocyte Membranes ◽  
Strain Rates ◽  
Rbc Membrane ◽  
Linear Behavior ◽  
Spectrin Network

Biological membranes are vital components of living cells as they function to maintain the structural integrity of the cells. Red blood cell (RBC) membrane comprises the lipid bilayer and the cytoskeleton network. The lipid bilayer consists of phospholipids, integral membrane proteins, peripheral proteins and cholesterol. It behaves as a 2D fluid. The cytoskeleton is a network of spectrin tetramers linked at the actin junctions. It is connected to the lipid bilayer primarily via Band-3 and ankyrin proteins. In this paper, we introduce a coarse-grained model with high computational efficiency for simulating a variety of dynamic and topological problems involving erythrocyte membranes. Coarse-grained agents are used to represent a cluster of lipid molecules and proteins with a diameter on the order of lipid bilayer thickness and carry both translational and rotational freedom. The membrane cytoskeleton is modeled as a canonical exagonal network of entropic springs that behave as Worm-Like-Chains (WLC). By simultaneously invoking these characteristics, the proposed model facilitates simulations that span large length-scales (∼ μm) and time-scales (∼ ms). The behavior of the model under shearing at different rates is studied. At low strain rates, the resulted shear stress is mainly due to the spectrin network and it shows the characteristic non-linear behavior of entropic networks, while the viscosity of the fluid-like lipid bilayer contributes to the resulting shear stress at higher strain rates. The apparent ease of this model in combining the spectrin network with the lipid bilayer presents a major advantage over conventional continuum methods such as finite element or finite difference methods for cell membranes.

Constitutive Modeling of the Finite Deformation Behavior of Membranes Possessing a Triangulated Network Microstructure

2005 ◽  
Vol 73 (4) ◽  
pp. 536-543 ◽  
Author(s):  
M. Arslan ◽  
M. C. Boyce
Keyword(s):  
Blood Cell ◽  
Mechanical Behavior ◽  
Lipid Bilayer ◽  
Red Blood Cell ◽  
Finite Deformation ◽  
Constitutive Modeling ◽  
Strain Energy ◽  
Shear Loading ◽  
Stress Strain ◽  
Spectrin Network

The mechanical behavior of the membrane of the red blood cell is governed by two primary microstructural features: the lipid bilayer and the underlying spectrin network. The lipid bilayer is analogous to a two-dimensional fluid in that it resists changes to its surface area, yet poses little resistance to shear. A skeletal network of spectrin molecules is cross-linked to the lipid bilayer and provides the shear stiffness of the membrane. Here, a general continuum level constitutive model of the large stretch behavior of the red blood cell membrane that directly incorporates the microstructure of the spectrin network is developed. The triangulated structure of the spectrin network is used to identify a representative volume element (RVE) for the model. A strain energy density function is constructed using the RVE together with various representations of the underlying molecular chain force-extension behaviors where the chain extensions are kinematically determined by the macroscopic deformation gradient. Expressions for the nonlinear finite deformation stress-strain behavior of the membrane are obtained by proper differentiation of the strain energy function. The stress-strain behaviors of the membrane when subjected to tensile and simple shear loading in different directions are obtained, demonstrating the capabilities of the proposed microstructurally detailed constitutive modeling approach in capturing the small to large strain nonlinear, anisotropic mechanical behavior. The sources of nonlinearity and evolving anisotropy are delineated by simultaneous monitoring of the evolution in microstructure including chain extensions, forces and orientations as a function of macroscopic stretch. The model captures the effect of pretension on the mechanical response where pretension is found to increase the initial modulus and decrease the limiting extensibility of the networked membrane.

Sign in / Sign up

Export Citation Format

Share Document