A5061229790- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Cardiomyopathy and Myosin Studies
- Photosynthetic Processes and Mechanisms
- Cellular Mechanics and Interactions
- Micro and Nano Robotics
- Protist diversity and phylogeny
- Muscle Physiology and Disorders
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Force Microscopy Techniques and Applications
- Fungal and yeast genetics research
- Advanced Electron Microscopy Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Organizational Management and Innovation
- Microfluidic and Bio-sensing Technologies
- 14-3-3 protein interactions
- Nuclear Structure and Function
- Genetic Neurodegenerative Diseases
- Plant Molecular Biology Research
- Nanofabrication and Lithography Techniques
- Advanced Materials and Mechanics
- Genomics and Chromatin Dynamics
University of Warwick
2016-2025
Yale University
2018
University of Virginia
2012
Marie Curie
2000-2009
MRC Laboratory of Molecular Biology
1988-2007
Medical Research Council
1988-2007
Accenture (United States)
2006
Institut de Biologie Structurale
2002
Centre National de la Recherche Scientifique
2002
Institut de Chimie
2002
Kinesin-1 is a molecular transporter that trafficks along microtubules. There some evidence kinesin-1 targets specific cellular sites, but it unclear how this spatial regulation achieved. To investigate process, we used combination of in vivo imaging kinesin heavy-chain Kif5c (an isoform kinesin-1) fused to GFP, vitro analyses and mathematical modelling. GFP-Kif5c fluorescent puncta localised subset microtubules live cells. These moved at speeds up 1 μm second–1 exchanged into cortically...
The microtubule-dependent kinesin-like protein Eg5 from Homo sapiens is involved in the assembly of mitotic spindle. It shows a three-domain structure with an N-terminal motor domain, central coiled coil, and C-terminal tail domain. In vivo HsEg5 reversibly inhibited by monastrol, small cell-permeable molecule that causes cells to be arrested mitosis. Both monomeric dimeric constructs have been examined order define minimal monastrol binding domain on HsEg5. NMR relaxation experiments show...
The N-terminal head domain of human dystrophin has been expressed in soluble form and high yield E. coli, allowing us to test the previously unconfirmed assumption that binds actin. DMD246, first 246 amino acid residues dystrophin, F-actin a strongly co-operative manner with Hill constant 3.5, but does not bind G-actin. Dystrophin heads are thus functionally competent actin-binding proteins. This result opens way identifying critical site encourages other domains might also be treated as...
Calponin and caldesmon are two thin filament-binding proteins found in smooth muscle that have both been attributed a role modulating the interaction of actin myosin. Using high-resolution dual-label immunocytochemistry we determined distribution calponin relative to contractile cytoskeletal compartments cell. We show, using chicken gizzard muscle, occurs cytoskeleton, with beta-cytoplasmic actin, filamin desmin, as well apparatus, myosin caldesmon. According observed labelling intensities,...
Kinesin and ncd motor proteins are homologous in sequence yet move opposite directions along microtubules. We have previously shown that monomeric kinesin bind the same orientation on equivalent sites relative to ends of tubulin sheets known polarity. now report cryoelectron microscope images 16-protofilament microtubules decorated with both single- double-headed ncd. Three-dimensional density maps difference show that, adenosine 5'-[beta,gamma-imido]triphosphate, dimeric motors tightly via...
Kinesin-1 is a two-headed molecular motor that walks along microtubules, with each step gated by adenosine triphosphate (ATP) binding. Existing models for the gating mechanism propose role microtubule lattice. We show unpolymerized tubulin binds to kinesin-1, causing tubulin-activated release of diphosphate (ADP). With no added nucleotide, kinesin-1 dimer one heterodimer. In adenylyl-imidodiphosphate (AMP-PNP), nonhydrolyzable ATP analog, two heterodimers. The data reveal an gate operates...
Summary Roughly half of all animal somatic cell spindles assemble by the classical prophase pathway, in which centrosomes separate ahead nuclear envelope breakdown (NEBD). The remainder prometaphase following NEBD. Why cells use dual pathway spindle assembly is unclear. Here, examining timing NEBD relative to onset Eg5-mEGFP loading centrosomes, we show that a time window 9.2 ± 2.9 min available for Eg5-driven centrosome separation NEBD, and those succeed separating their within this...
Recent studies have shown that the targeting of substrate adhesions by microtubules promotes adhesion site disassembly (Kaverina, I., O. Krylyshkina, and J.V. Small. 1999. J. Cell Biol. 146:1033–1043). It was accordingly suggested serve to convey a signal sites modulate their turnover. Because microtubule motors would be most likely candidates for effecting transmission, we investigated consequence blocking motor activity on dynamics. Using function-blocking antibody as well dynamitin...