A5046977519- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Connective tissue disorders research
- Cell Adhesion Molecules Research
- Cardiomyopathy and Myosin Studies
- 14-3-3 protein interactions
- Hippo pathway signaling and YAP/TAZ
- Skin and Cellular Biology Research
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Blood properties and coagulation
- Signaling Pathways in Disease
- Lipid Membrane Structure and Behavior
- Nuclear Structure and Function
- Urban Transport and Accessibility
- Advanced Fluorescence Microscopy Techniques
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- RNA regulation and disease
- Transportation Planning and Optimization
- Surface Modification and Superhydrophobicity
Tianjin University
2017-2025
Kitami Institute of Technology
2024
The University of Tokyo
2021-2024
Tianjin University of Science and Technology
2024
Nara Prefecture General Medical Center
2021
Brigham and Women's Hospital
2007-2016
Harvard University
2007-2016
Nagoya Institute of Technology
2012
Yokohama National University
1999-2012
Sapporo Kosei General Hospital
2009
We show that actin filaments, shortened to physiological lengths by gelsolin and cross-linked with recombinant human filamins (FLNs), exhibit dynamic elastic properties similar those reported for live cells. To achieve elasticity values of comparable magnitude cells, the in vitro network must be subjected external prestress, which directly controls elasticity. A molecular requirement strain-related behavior at conditionsis a flexible hinge found FLNa some FLNb molecules. Basic physical...
We describe an active polymer network in which processive molecular motors control elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted bipolar muscle myosin II. The stiffen the more than two orders magnitude pulling on anchored FLNa cross-links, thereby generating internal stress. stiffening response closely mimics effects external stress applied mechanical shear. Both stresses can drive into a highly nonlinear, stiffened regime. reaches values...
Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to cerebral cortex and cause cardiovascular defects. Complete loss of Flna mice results embryonic lethality with severe cardiac structural defects involving ventricles, atria, outflow tracts, as well widespread aberrant vascular patterning. Despite these developmental defects, motility many cell types does not appear be affected. Instead, Flna-null embryos display abnormal epithelial endothelial organization adherens...
Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family binding domains (ABDs) an elongated flexible segment 24 immunoglobulin (Ig) repeats. We generated a library fragments to examine their define the structural properties that enable its various functions. find Ig repeats 9–15 contain F-actin–binding domain necessary for high avidity binding. 16–24, where most FLNa-binding partners interact, do...
Actin-binding proteins (ABPs) regulate the assembly of actin filaments (F-actin) into networks and bundles that provide structural integrity cell. Two these ABPs, filamin alpha-actinin, have been extensively used to model mechanical properties grown in vitro; however, there is a lack understanding how molecular interactions between ABPs F-actin dynamic cytoskeleton. Here, we present native-like assay geometry test rupture force complex formed by an ABP linking two quasiparallel filaments. We...
The phosphorylation and localization of the membrane-linking protein moesin was analyzed during early activation platelets with thrombin. Activated elaborate filopodia spread to assume flat pancake-like shapes, is localized in cell body. In resting platelets, approximately 25% molecules are phosphorylated as shown by metabolic labeling 32P(i) isoelectric focusing. Within seconds after exposure thrombin, increases, reaching a maximum 35% labeled 1 min, followed decrease new basal level within...
Networks of filamentous actin cross-linked with the actin-binding protein filamin $A$ exhibit remarkable strain stiffening leading to an increase in differential elastic modulus by several orders magnitude over linear value. The variation frequency dependence and loss moduli as a function prestress is consistent that observed living cells, suggesting cell elasticity always measured nonlinear regime, essential control parameter.
Alpha-actinin-4 is a widely expressed protein that employs an actin-binding site with two calponin homology domains to crosslink actin filaments (F-actin) in Ca(2+)-sensitive manner vitro. An inherited, late-onset form of kidney failure caused by point mutations the alpha-actinin-4 domain. Here we show alpha-actinin-4/F-actin aggregates, observed vivo podocytes humans and mice disease, likely as direct result increased affinity protein. We document exposure buried 1 mutant causes increase...
Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL...
Activation of human platelets with thrombin transiently increases phosphorylation at 558 threonine moesin as determined state-specific antibodies. This specific modification is completely inhibited by the kinase inhibitor staurosporine and maximally promoted phosphatase calyculin A, making it possible to purify two forms homogeneity. Blot overlay assays F-actin probes labeled either [ 32 P]ATP or 125 I show that only phosphorylated interacts in total platelet lysates, antibody...
Cell adhesion and spreading are regulated by complex interactions involving the cytoskeleton extracellular matrix proteins. We examined interaction of intermediate filament protein vimentin with actin cross-linking filamin A in regulation HEK-293 3T3 cells. Filamin vimentin-expressing cells were well spread on collagen exhibited numerous cell extensions enriched vimentin. By contrast, treated small interfering RNA (siRNA) to knock down or poorly spread; both these populations >50% reductions...
The cellular prion protein (PrP) is a highly conserved, widely expressed, glycosylphosphatidylinositol-anchored (GPI-anchored) cell surface glycoprotein. Since its discovery, most studies on PrP have focused role in neurodegenerative diseases, whereas function outside the nervous system remains unclear. Here, we report that human pancreatic ductal adenocarcinoma (PDAC) lines expressed PrP. However, was neither glycosylated nor GPI-anchored, existing as pro-PrP and retaining GPI anchor...
Networks of the biopolymer actin, cross-linked by compliant protein filamin, form soft gels. They can, however, withstand large shear stresses due to their pronounced nonlinear elastic behavior. The elasticity can be controlled varying number cross-links per actin filament. We propose and test a model rigid filaments decorated multiple flexible linkers that is in quantitative agreement with experiment. This allows us estimate loads on individual cross-links, which we find less than 10 pN.