Although they have been advocated with an understandable enthusiasm, mitosis-specific agents such as inhibitors of mitotic kinases and kinesin spindle protein have not been successful clinically. These drugs were developed as agents that would build on the success of microtubule-targeting agents while avoiding the neurotoxicity that encumbers drugs such as taxanes and vinca alkaloids. The ratio...

Transport of intracellular cargos along microtubules is essential for the function and survival eukaryotic cells. While we know much about motors which perform this transport, significantly less known how transport controlled directed. One step process remains little understood binding to microtubules. In poster, explore what we’ve learned through several recent studies. We look at in different...

Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated and nucleation from surface of other microtubules mediated augmin complex. Impairment in apical progenitors developing mouse brain induces p53-dependent apoptosis causes non-lethal microcephaly. Whether disruption non-centrosomal has similar effects is unclear. Here, we show, using embryos...

Abstract The cytoskeleton is a major focus of physical studies to understand organization inside cells given its primary role in cell motility, division, and mechanics. Recently, protein condensation has been shown be another intracellular organizational strategy. Here, we report that the microtubule crosslinking proteins, MAP65-1 PRC1, can form phase separated condensates at physiological salt...

The effects of inhibitors of mitosis, energy metabolism and protein synthesis on clot retraction were investigated. The results show that (1) Incubation of colchicine (0-01-0-1 mM) with platelet-rich plasma (PRP) inhibits the subsequent retraction of clots derived from diluted PRP. (2) Inhibition of clot retraction by high concentrations of colchicine (up to 40 mM) can be overcome by increasing...

The negative surface charge of human granulocytes was diminished after incubation with the chemotactic factors C5a, dialyzable transfer factor, and the enzymes kallikrein and plasminogen activator. No such change was observed after incubation with human IgG, albumin, horeseradish peroxidase, or a mixture of prekallikrein and plaminogen proactivator. Hydrocortisone inhibited the effect of C5a up...

To identify novel proteins regulating the microtubule cytoskeleton, we screened a library of purine derivatives using mitotic spindle assembly in Xenopus egg extracts as an assay. Out of a collection of 1561 compounds, we identified 15 that destabilized microtubules without targeting tubulin directly, resulting in small spindles. Affinity chromatography with one compound, named diminutol, revea...

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assem...

Epidermal hypocotyl cells are characterized by a highly structured cortical microtubule array, consisting of bundles of polarized, parallel microtubules that gradually migrate across the cortex in a rotary fashion (Chan et al., 2007). In animal cells, microtubules arise from centrosomes; however, plant cells lack centrosomes, and microtubules are thought to self-organize into structured arrays ...