Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.

The excessive inflammation caused by the prolonged activation of Toll-like receptor 4 (TLR4) and its downstream signaling pathways leads to sepsis. CD14-mediated endocytosis of TLR4 is the key step to control the amount of TLR4 on cell membrane and the activity of downstream pathways. The actin cytoskeleton is necessary for receptor-mediated endocytosis, but its role in TLR4 endocytosis remains elusive.

Tropomodulin1 Expression Increases Upon Maturation in Dendritic Cells and Promotes Their Maturation and Immune Functions.

Dendritic cells (DCs) are the most potent antigen-presenting cells. Upon maturation, DCs express costimulatory molecules and migrate to the lymph nodes to present antigens to T cells. The actin cytoskeleton plays key roles in multiple aspects of DC functions.

Water transport and homeostasis as a major function of erythrocytes.

Erythrocytes have long been known to change volumes and shapes in response to different salt concentrations. Aquaporin-1 (AQP1) was discovered in their membranes more than 20 yr ago. The physiological roles of volume changes and AQP1 expression, however, have remained unclear.

Fluid Shear Stress Upregulates E-Tmod41 via miR-23b-3p and Contributes to F-Actin Cytoskeleton Remodeling during Erythropoiesis.

The membrane skeleton of mature erythrocyte is formed during erythroid differentiation. Fluid shear stress is one of the main factors that promote embryonic hematopoiesis, however, its effects on erythroid differentiation and cytoskeleton remodeling are unclear. Erythrocyte tropomodulin of 41 kDa (E-Tmod41) caps the pointed end of actin filament (F-actin) and is critical for the formation of hexagonal topology of erythrocyte membrane skeleton.

Cell type-restricted expression of erythrocyte tropomodulin Isoform41 in exon 1 knockout/LacZ knock-in heterozygous mice.

Full-length erythrocyte tropomodulin (E-Tmod or Tmod1) isoform of 41 kDa is an actin nucleation protein and caps the pointed end of tropomyosin-coated actin filaments. It participates in the length control of short actin protofilaments in the erythrocyte membrane skeletal network as well as the organization of microfilaments in non-erythroid cells. Recently we discovered and characterized a truncated isoform of 29 kDa, which lacks the N-terminal sequence encoded by exons 1 and 2 required for nucleation and capping.

Effect of N-ethylmaleimide, chymotrypsin, and H₂O₂ on the viscoelasticity of human erythrocytes: experimental measurement and theoretical analysis.

The physiological functions of erythrocytes depend critically on their morphology, deformability, and aggregation capability in response to external physical and chemical stimuli. The dynamic deformability can be described in terms of their viscoelasticity. We applied jumping optical tweezers to trap and stretch individual red blood cells (RBCs) to characterize its viscoelasticity in terms of the Young's modulus and viscosity by analyzing the experimental data of dynamic deformation using a 2-parameter Kelvin solid model.

RGD-containing ankyrin externalized onto the cell surface triggers αVβ3 integrin-mediated erythrophagocytosis.

The RGD motif on the extracellular matrix or cell surface, together with its integrin receptors, constitutes a major recognition system for cell adhesion. There are several erythrocyte major membrane skeletal proteins, e.g.

Erythrocyte tropomodulin isoforms with and without the N-terminal actin-binding domain.

Erythrocyte tropomodulin (E-Tmod or Tmod1) of 41 kDa is a tropomyosin (TM)-binding protein that caps the slow-growing end of the actin filaments. Its N-terminal half is flexible, whereas the C-terminal half has a single domain structure. E-Tmod/TM5 complex may function as a "molecular ruler" generating actin protofilaments of ∼37 nm.

Nanomechanics of multiple units in the erythrocyte membrane skeletal network.

Erythrocytes undergo deformations when they transport O(2) and CO(2) across the membrane, yet the 3D nanomechanics of the skeletal network remains poorly understood. Expanding from our previous single isolated unit, we now simulate networks consisting of 1-10 concentric rings of repeating units in equibiaxial deformation. The networks are organized with (1) a 3D model for a single unit, (2) a wrap-around mode between Sp and actin protofilament in the intra-unit interaction, and (3) a random inter-unit connectivity.

Oxidized low-density lipoprotein (Ox-LDL) impacts on erythrocyte viscoelasticity and its molecular mechanism.

The oxidized low-density lipoprotein (Ox-LDL) plays an important role in atherosclerosis, yet it remains unclear if it damages circulating erythrocytes. In this study, erythrocyte deformability and its membrane proteins after Ox-LDL incubations are investigated by micropipette aspiration, thiol radical measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability, decreases free thiol radical contents in erythrocytes, and induces the cross-linking among membrane proteins.

Specific expression of E-Tmod (Tmod1) in horizontal cells: implications in neuronal cell mechanics and glaucomatous retina.

Erythrocyte tropomodulin (E-Tmod) is a tropomyosin-binding and actin capping protein at the point end of the filaments. It is part of a molecular ruler that plays an important role in generating short actin protofilaments critical for the integrity of the cell membrane. Here, with the use of E-Tmod+/lacZ mice, we demonstrated a specific E-Tmod expression in horizontal cells (HCs) in the retina, and analyzed the stress-strain relationship of HCs, vertically oriented neurons, and retinal ganglial cells (RGC) under normal and high intraocular pressure (IOP).

The influence of fluid shear stress on the remodeling of the embryonic primary capillary plexus.

The primary capillary plexus in early yolk sacs is remodeled into matured vitelline vessels aligned in the direction of blood flow at the onset of cardiac contraction. We hypothesized that the influence of fluid shear stress on cellular behaviors may be an underlying mechanism by which some existing capillary channels remain open while others are closed during remodeling. Using a recently developed E-Tmod knock-out/lacZ knock-in mouse model, we showed that erythroblasts exhibited rheological properties similar to those of a viscous cell suspension.

Mapping the tropomyosin isoform 5 binding site on human erythrocyte tropomodulin: further insights into E-Tmod/TM5 interaction.

Actin protofilaments in the erythrocyte membrane skeleton are uniformly approximately 37nm. This length may be in part attributed to a "molecular ruler" made of erythrocyte tropomodulin (E-Tmod) and tropomyosin (TM) isoforms 5 or 5b. We previously mapped the E-Tmod binding site to TM5 N-terminal heptad repeat residues "a" (I(7), I(14)), "d" (V(10)) and "f" (R(12)).

3-D nanomechanics of an erythrocyte junctional complex in equibiaxial and anisotropic deformations.

The erythrocyte membrane skeleton deforms constantly in circulation, but the mechanics of a junctional complex (JC) in the network is poorly understood. We previously proposed a 3-D mechanical model for a JC (Sung, L. A.

Protofilament and hexagon: a three-dimensional mechanical model for the junctional complex in the erythrocyte membrane skeleton.

It is a long-standing mystery why erythrocyte actin filaments in the junctional complex (JC) are uniformly approximately 37 nm and the membrane skeleton consists of hexagons. We have previously proposed that a "molecular ruler" formed by E-tropomodulin and tropomyosin 5 or 5b functions to generate protofilaments of 12 G actin under mechanical stress. Here, we illustrate that intrinsic properties of actin filaments, e.

E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation.

Tropomodulins are a family of proteins that cap the slow-growing end of actin filaments. Erythrocyte tropomodulin (E-Tmod) stabilizes short actin protofilaments in erythrocytes and caps longer sarcomeric actin filaments in striated muscles. We report the knockin of the beta-galactosidase gene (LacZ) under the control of the endogenous E-Tmod promoter and the knockout of E-Tmod in mouse embryonic stem cells.