A5089071903- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Genetic and Kidney Cyst Diseases
- Linguistics and Discourse Analysis
- 14-3-3 protein interactions
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Cardiomyopathy and Myosin Studies
- Glycosylation and Glycoproteins Research
- Retinal Development and Disorders
- Cancer Treatment and Pharmacology
- Wnt/β-catenin signaling in development and cancer
- Protein Structure and Dynamics
- Philosophy and Theoretical Science
- Autophagy in Disease and Therapy
- Historical Linguistics and Language Studies
- Erythrocyte Function and Pathophysiology
Columbia University
2012-2024
Columbia University Irving Medical Center
2009-2024
Université de Moncton
2006-2014
Hope Center for Neurological Disorders
2012
University College London
1991-2012
Cedars-Sinai Medical Center
2012
Wayne State University
2012
MRC Prion Unit
2012
University Physicians
2011
City of Hope
2009
Dynactin is a multisubunit complex that plays an accessory role in cytoplasmic dynein function. Overexpression mammalian cells of one dynactin subunit, dynamitin, disrupts the complex, resulting dissociation from prometaphase kinetochores, with consequent perturbation mitosis (Echeverri, C.J., B.M. Paschal, K.T. Vaughan, and R.B. Vallee. 1996. J. Cell Biol. 132:617–634). Based on these results, was proposed to play linking kinetochores and, potentially, membrane organelles. The current study...
Dynactin is a multi-subunit complex which has been implicated in cytoplasmic dynein function, though its mechanism of action unknown. In this study, we have characterized the 50-kD subunit dynactin, and analyzed effects overexpression on mitosis living cells. Rat human cDNA clones revealed p50 to be novel highly conserved, containing three predicted coiled-coil domains. Immunofluorescence staining dynactin components cultured vertebrate cells showed that both complexes are recruited...
We observe that one of the high molecular mass microtubule-associated proteins (MAPs) from brain exhibits nucleotide-dependent binding to microtubules. identify protein as MAP IC, which was previously described in this laboratory a minor component standard microtubule preparations (Bloom, G.S., T. Schoenfeld, and R.B. Vallee, 1984, J. Cell Biol., 98:320-330). find 1C is enriched microtubules prepared absence nucleotide. Kinesin also found these preparations, but can be specifically extracted...
The effect of the antimitotic drug taxol on association MAPs (microtubule-associated proteins) with microtubules was investigated. Extensive microtubule assembly occurred in presence Taxol at 37 degrees C. 0 C, and C 0.35 M NaCl, overcoming inhibition normally observed under latter two conditions. At complete both tubulin Taxol. However, elevated ionic strength, only assembled, forming devoid MAPs. could also be released from surface preformed by exposure to strength. These properties...
Cytoplasmic dynein is a retrograde microtubule motor thought to participate in organelle transport and some aspects of minus end-directed chromosome movement. The mechanism binding organelles kinetochores unknown. Based on homology with the Chlamydomonas flagellar outer arm intermediate chains (ICs), we proposed role for cytoplasmic ICs linking protein kinetochores. In this study two different IC isoforms were used blot overlay immunoprecipitation assays identify IC-binding partners....
Mutations in the human LIS1 gene cause smooth brain disease classical lissencephaly. To understand underlying mechanisms, we conducted situ live cell imaging analysis of function throughout entire radial migration pathway. In utero electroporation small interference RNA and short hairpin dominant negative dynactin cDNAs caused a dramatic accumulation multipolar progenitor cells within subventricular zone embryonic rat brains. This effect resulted from complete failure progression to...
We have found that a CAMP-dependent protein kinase present in brain microtubule preparations co-purifies with microtubule-associated 2 (MAP 2)
The ability of gliomas to invade the brain limits efficacy standard therapies. In this study, we have examined glioma migration in living tissue by using two novel vivo model systems. Within brain, cells migrate like nontransformed, neural progenitor cells-extending a prominent leading cytoplasmic process followed burst forward movement cell body that requires myosin II. contrast, on two-dimensional surface, more fibroblasts, and they do not require II move. To explain phenomenon, studied...
After fusion of the viral envelope with plasma membrane, herpes simplex virus type 1 (HSV1) capsids are transported along microtubules (MTs) from cell periphery to nucleus. The motor ATPase cytoplasmic dynein and its multisubunit cofactor dynactin mediate most transport processes directed toward minus-ends MTs. Immunofluorescence microscopy experiments demonstrated that HSV1 colocalized dynactin. We blocked function by overexpressing subunit dynamitin, which leads disruption complex. then...
Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, participates cytoplasmic dynein-mediated nuclear migration. We previously reported that mammalian functions cell division and coimmunoprecipitates with dynein dynactin. also localized to cortex kinetochores mitotic cells, known sites action. now find COOH-terminal WD repeat region is sufficient for kinetochore targeting....