A5084697894- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Protist diversity and phylogeny
- Photosynthetic Processes and Mechanisms
- Cellular Mechanics and Interactions
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Glioma Diagnosis and Treatment
- Plant Molecular Biology Research
- Diatoms and Algae Research
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- 14-3-3 protein interactions
- Cancer-related Molecular Pathways
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Cell Image Analysis Techniques
- Genetics, Bioinformatics, and Biomedical Research
- Advanced Proteomics Techniques and Applications
- Reproductive Biology and Fertility
- Glycosylation and Glycoproteins Research
- Cardiomyopathy and Myosin Studies
University of Washington
2016-2025
Seattle University
1996-2019
University of Calgary
2015
Friday Harbor Laboratories
2008-2011
Howard Hughes Medical Institute
2010
Institute of Molecular Biology and Biophysics
2010
University of Hawaii System
1995
University of California, San Francisco
1989-1993
University of California, Berkeley
1986-1993
In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized nomenclature based on 14 family designations. The scheme unifies all previous phylogenies proposals, while allowing individual sequence names remain same, for expansion occur as new sequences are discovered.
Using antipeptide antibodies to conserved regions of the kinesin motor domain, we cloned a kinesin-related protein that associates with centromere region mitotic chromosomes. We call MCAK, for centromere-associated kinesin. MCAK appears concentrated on centromeres at prophase and persists until telophase, after which time localization disperses. It is found throughout between kinetochore plates isolated CHO chromosomes, in contrast two other kinetochore-associated microtubule motors:...
In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of α-tubulin. The significance this selective detyrosination MTs is not understood. study, we report that tubulin in fibroblasts inhibits MT disassembly. This inhibition relieved overexpression depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression MCAK expression prevents disassembly normal tyrosinated fibroblasts. Detyrosination...
Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes addition of a C-terminal tyrosine residue to α-tubulin in tubulin tyrosination cycle, is involved tumor progression and has vital role neuronal organization. We show mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 other microtubule plus-end tracking proteins comprising cytoskeleton-associated glycine-rich (CAP-Gly) binding domain such as CLIP-115 p150 Glued, localize ends tyrosinated microtubules but not detyrosinated...
Mitotic centromere-associated kinesin (MCAK) is recruited to the centromere at prophase and remains associated until after telophase. MCAK a homodimer that encoded by single gene has no subunits. A motorless version of binds centromeres but not microtubules disrupts chromosome segregation during anaphase. Antisense-induced depletion results in same defect. overexpression induces centromere-independent bundling eventual loss spindle microtubule polymer suggesting and/or depolymerization...
The human genome has three unique genes coding for kinesin-13 proteins called Kif2a, Kif2b, and MCAK (Kif2c). Kif2a have documented roles in mitosis, but the function of Kif2b not been defined. Here, we show that is expressed at very low levels cultured cells GFP-Kif2b localizes predominately to centrosomes midbodies, also spindle microtubules transiently kinetochores. Kif2b-deficient assemble monopolar or disorganized spindles. Chromosomes typical kinetochore-microtubule attachments,...
The coupling of kinetochores to dynamic spindle microtubules is crucial for chromosome positioning and segregation, error correction, cell cycle progression. How these fundamental attachments are made persist under tensile forces from the remain important questions. As microtubule-binding elements, budding yeast Ndc80 Dam1 kinetochore complexes essential not redundant, but their distinct contributions unknown. In this study, we show that complex a processivity factor complex, enhancing...
Metaphase chromosome positioning depends on Kif18A, a kinesin-8 that accumulates at and suppresses the dynamics of K-MT plus ends. By engineering Kif18A mutants suppress MT but fail to concentrate ends, we identify mechanism allows accumulate ends level required movements. Enrichment its C-terminal tail domain, while ability growth is conferred by N-terminal motor domain. The contains second MT-binding domain diffuses along lattice, suggesting it tethers track. Consistently, enhances...
We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this design that assemble into micrometer-scale with wide range of geometries in vivo vitro. Cryo-electron microscopy structures six designs are close the models. The filament building blocks idealized repeat proteins, thus diameter can be systematically tuned by varying number units. assembly disassembly controlled engineered anchor capping units built monomers lacking...
ABSTRACT To identify kinesin-related proteins that may be important for mitotic function in embryonic and tissue culture cells we have generated polyclonal antibodies to two synthetic peptides corresponding conserved regions of the kinesin motor domain. In Xenopus eggs identified a family microtubule-binding proteins, recognized by one or both affinity-purified peptide but not monoclonal recognize conventional heavy chain. Like kinesin, most these bind microtubules only upon addition AMP-PNP...
Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerizer that consistent with its role in promoting chromosome segregation during mitosis. Here we show the conserved motor domain of MCAK necessary but not sufficient for depolymerization cells or vitro. The addition only 30 amino acids N-terminal to restores activity. Furthermore, dimerization studies revealed smallest functional deletion constructs are monomers. These results define highly within and related (KIN I)...
MCAK is a member of the kinesin-13 family microtubule (MT)-depolymerizing kinesins. We show that potent MT depolymerizer tracks (treadmills) with tips polymerizing MTs in living cells. Tip tracking inhibited by phosphorylation and dependent on extreme COOH-terminal tail MCAK. not essential for MCAK's MT-depolymerizing activity. propose tip mechanism which preferentially localized to regions cell modulate plus ends MTs.