A5075446824- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Biotin and Related Studies
- Force Microscopy Techniques and Applications
- Cell Adhesion Molecules Research
- Axon Guidance and Neuronal Signaling
- Hippo pathway signaling and YAP/TAZ
- Virus-based gene therapy research
- Fungal and yeast genetics research
- Heat shock proteins research
- Neurogenesis and neuroplasticity mechanisms
- Advanced Fluorescence Microscopy Techniques
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Marine and coastal ecosystems
- Photosynthetic Processes and Mechanisms
- Tissue Engineering and Regenerative Medicine
- Genetics, Aging, and Longevity in Model Organisms
- Receptor Mechanisms and Signaling
- Retinal Development and Disorders
- 3D Printing in Biomedical Research
- Reproductive System and Pregnancy
University of Pittsburgh
2013-2025
Akademia Pomorska w Słupsku
2021
Massachusetts Institute of Technology
2000-2016
Stanford University
2007-2013
Centrum Onkologii
2012
Center for Cancer Research
2007
Cornell University
1996-1997
Tuba is a novel scaffold protein that functions to bring together dynamin with actin regulatory proteins. It concentrated at synapses in brain and binds selectively through four N-terminal Src homology-3 (SH3) domains. variety of proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, Ena/VASP via C-terminal SH3 domain. Direct binding partners include N-WASP Forced targeting the domain mitochondrial surface can promote accumulation F-actin around mitochondria. A Dbl homology present...
αE-catenin binds the cell–cell adhesion complex of E-cadherin and β-catenin (β-cat) regulates filamentous actin (F-actin) dynamics. In vitro, binding to E-cadherin–β-cat lowers affinity for F-actin, alone can bind F-actin inhibit Arp2/3 complex–mediated polymerization. cells, test whether dynamics independently cadherin complex, cytosolic pool was sequestered mitochondria without affecting overall levels or cadherin–catenin complex. Sequestering alters lamellipodia architecture increases...
Planar cell polarity (PCP) regulates alignment required for collective movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question role cilium PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and movement, but underlying mechanism is unknown. Here we show Wdpcp can by direct modulation actin cytoskeleton. These studies were made possible recovery...
Proteins of the Ena/VASP family are implicated in processes that require dynamic actin remodeling such as axon guidance and platelet activation. In this work, we explored some pathways likely regulate dynamics part via EVL (Ena/VASP-like protein). Two isoforms, EVL-I, were highly expressed hematopoietic cells thymus spleen. CD3-activated T-cells, was found F-actin-rich patches at distal tips microspikes formed on activated side T-cells. Like other members, localized to focal adhesions...
The Ena/vasodilator-stimulated phosphoprotein (VASP) protein family is implicated in the regulation of a number actin-based cellular processes, including lamellipodial protrusion necessary for whole cell translocation. A growing body evidence derived largely from vitro biochemical experiments using purified proteins, cell-free extracts, and pathogen motility has begun to suggest various mechanistic roles Ena/VASP proteins control actin dynamics. Using complementation phenotypes...
Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are key actin regulators that localize at regions of dynamic remodeling, including cellular protrusions and cell–cell cell–matrix junctions. Several studies have suggested Ena/VASP involved in the formation function Here, we establish importance endothelial junctions vivo by analysis Ena/VASP-deficient animals. In absence Ena/VASP, vasculature exhibits patterning defects lacks structural integrity, leading to edema,...
The actin-binding protein αE-catenin may contribute to transitions between cell migration and cell–cell adhesion that depend on remodeling the actin cytoskeleton, but underlying mechanisms are unknown. We show domain (ABD) binds cooperatively individual filaments binding is accompanied by a conformational change in protomer affects filament structure. ABD limits barbed-end growth, especially bundles. inhibits branching Arp2/3 complex severing cofilin, both of which contact regions...
The ternary complex of cadherin, β-catenin, and α-catenin regulates actin-dependent cell–cell adhesion. α-Catenin can bind β-catenin F-actin, but in mammals either binds as a monomer or F-actin homodimer. It is not known if this conformational regulation evolutionarily conserved. Caenorhabditis elegans homolog HMP-1 essential for epidermal enclosure embryo elongation. Here we show that with functional C-terminal binding domain. However, neither full-length nor...
CNS synapse assembly typically follows after stable contacts between “appropriate” axonal and dendritic membranes are made. We show that presynaptic boutons selectively form de novo following neuronal fiber adhesion to beads coated with poly- d -lysine (PDL), an artificial cationic polypeptide. As demonstrated by atomic force live confocal microscopy, functional self-assemble as rapidly 1 h bead contact, found contain a variety of proteins characteristic endings. Interestingly, compartment...
Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive stimulate actin polymerization in neuronal growth cones whereas repulsive induce disassembly. Contrary this model, we find cue Slit stimulates formation and elongation actin-based filopodia from mouse dorsal root ganglion cones....
ABSTRACT The junctional complexes that couple cardiomyocytes must transmit the mechanical forces of contraction while maintaining adhesive homeostasis. adherens junction (AJ) connects actomyosin networks neighboring and is required for proper heart function. Yet little known about molecular composition cardiomyocyte AJ or how it organized to function under load. Here, we define architecture, dynamics proteome AJ. Mouse neonatal assemble stable AJs along intercellular contacts with...
Nitrite reductase catalyzes the reduction of nitrite to nitric oxide, first step in denitrification produce a gaseous product. We have cloned gene nirK, which encodes copper-type from denitrifying variant Rhodobacter sphaeroides, strain 2.4.3. The deduced open reading frame has significant identity with other reductases. Analysis promoter region shows that transcription initiates 31 bases upstream translation start codon. initiation site is 43.5 downstream putative binding for...
During denitrification, freely diffusible nitric oxide (NO) is generated for use as a terminal electron acceptor. NO produced by nitrite reductase (Nir) and reduced to nitrous (Nor). Using Nir Nor-deficient mutants of Rhodobacter sphaeroides 2.4.3, we have shown that the endogenous production or addition exogenous induces transcription certain genes encoding Nor. A strain was found be capable expressing wild type levels nirK-lacZ norB-lacZ fusions in medium unamended with nitrogen oxides....
The adherens junction couples the actin cytoskeletons of neighboring cells to provide foundation for multicellular organization. core is cadherin-catenin complex that arose early in evolution multicellularity link intercellular adhesions. Over time, evolutionary pressures have shaped signaling and mechanical functions meet specific developmental physiological demands. Evolutionary rate covariation (ERC) identifies proteins with correlated fluctuations can reflect shared selective functions....
αT (Testes)-catenin, a critical factor regulating cell-cell adhesion in the heart, directly couples cadherin-catenin complex to actin cytoskeleton at intercalated disk (ICD), unique junction that cardiomyocytes. Loss of αT-catenin mice reduces plakophilin2 and connexin 43 recruitment ICD. Since is subjected mechanical stretch during actomyosin contraction cardiomyocytes, its activity could be regulated by force. To provide insight how force regulates function, we investigated stability...
Mechanical strain substantially influences tissue shape and function in various contexts from embryonic development to disease progression. Disruptions these processes can result congenital abnormalities short-circuit mechanotransduction pathways. Manipulating live tissues is crucial for understanding its impact on cellular subcellular activities, unraveling the interplay between mechanics cells. Existing tools, such as optogenetic modulation of strain, are limited small strains over...
It is unknown whether homologs of the cadherin·catenin complex have conserved structures and functions across Metazoa. Mammalian αE-catenin an allosterically regulated actin-binding protein that binds cadherin·β-catenin as a monomer whose dimerization potentiates F-actin association. We tested these functional properties are in another vertebrate, zebrafish Danio rerio. Here we show, despite 90% sequence identity, rerio Mus musculus striking differences. demonstrate D. monomeric by size...
Rhodobacter sphaeroides 2.4.1, which is incapable of denitrification, has been found to carry nnrR, the nor operon, and nnrS, are utilized for denitrification in R. 2.4.3. The gene encoding nitrite reductase was not 2.4.1. Expression beta-galactosidase activity from a norB-lacZ fusion activated when cells 2.4.1 were incubated with NO-producing bacteria. This result indicates that products nnrR genes flanking it growing an environment where occurs.
The adherens junction (AJ) couples the actin cytoskeletons of neighboring cells to allow mechanical integration and tissue organization. physiological demands intercellular adhesion require that AJ be responsive dynamic changes in force while maintaining load. These are tested heart, where cardiomyocyte AJs must withstand repeated cycles actomyosin-mediated contractile force. Here we show force-responsive recruit actin-binding ligands selectively couple networks. We employed a panel...