Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.4.4 (kinesin)
5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PC-3 human prostatic tumor sublines have been previously isolated which exhibit striking differences in their invasive and metastatic phenotypes. This work has been extended here to measure and compare the levels of kinesin, a microtubule-dependent translocator molecule, in the PC-3 sublines. Western blots, slot blots, radiolabeling, and immunoprecipitation analysis showed that kinesin was expressed in the highly invasive and metastatic sublines at levels which were elevated above the base-line levels observed in the parent PC-3 cells. In comparison, kinesin was not expressed in detectable amounts in the noninvasive cell lines. The conditioned medium of the metastatic PC-3 sublines contained a heat- and trypsin-sensitive protein which exhibited a dosage-dependent capacity to stimulate increased kinesin expression, type IV collagenase secretion, and invasion of Matrigel by the metastatic sublines. The noninvasive sublines failed to secrete a similar stimulatory factor(s) or respond to the conditioned medium of metastatic sublines. Various growth factors and cytokines tested (platelet-derived growth factor, epidermal growth factor, insulin-like growth factor, formylmethionineleucinephenylalanine) had no significant effect on either kinesin expression or protease secretion and invasion. Pertussis toxin blocked the stimulatory effects of the conditioned medium, but other agents known to interfere with adenylate cyclase pathways (i.e., cholera toxin, forskolin, 8-bromoadenosine) failed to block stimulation. The data show for the first time that kinesin, protease secretion, and the resulting invasion process may be regulated in a coordinated manner by an autocrine factor(s) which activates G-protein-dependent processes.
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PMID:Regulation of kinesin expression and type IV collagenase secretion in invasive human prostate PC-3 tumor sublines. 165 72

One of our monoclonal antibodies against the heavy chain of bovine kinesin (H2) also recognized the heavy chain of squid kinesin. The immunofluorescence pattern of H2 in axoplasm was similar to that seen in mammalian cells with antibodies specific for kinesin light and heavy chains, indicating that squid kinesin is also concentrated on membrane-bounded organelles. Although kinesin is assumed to be a motor for translocation of membrane-bounded organelles in fast axonal transport, direct evidence has been lacking. Perfusion of axoplasm with purified H2 at 0.1-0.4 mg/ml resulted in a profound inhibition of both the rates and number of organelles moving in anterograde and retrograde directions in the interior of the axoplasm, and comparable inhibition was noted in bidirectional movement along individual microtubules at the periphery. Maximal inhibition developed over 30-60 min. Perfusion with higher concentrations of H2 (greater than 1 mg of IgG per ml) were less effective, whereas perfusion with 0.04 mg of H2 per ml resulted in minimal inhibition. Movement of membrane-bounded organelles after perfusion with comparable levels of irrelevant mouse IgG (0.04 to greater than 1 mg/ml) were not distinguishable from perfusion with buffer controls. Inhibition of fast axonal transport by an antibody specific for kinesin provides direct evidence that kinesin is involved in the translocation of membrane-bounded organelles in axons. Moreover, the inhibition of bidirectional axonal transport by H2 raises the possibility that kinesin may play some role in both anterograde and retrograde axonal transport.
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PMID:A monoclonal antibody against kinesin inhibits both anterograde and retrograde fast axonal transport in squid axoplasm. 168 58

Contrary to the traditional view that microtubules pull chromosomes polewards during the anaphase stage of meiotic and mitotic cell divisions, new evidence suggests that the chromosome movements are driven by a motor located at the kinetochore. The process of chromosome segregation involves proper arrangement of kinetochores for spindle attachment, followed by spindle attachment and chromosome movement. Mechanisms in Drosophila for chromosome segregation in meiosis differ in males and females, implying the action of different gene products in the two sexes. A product encoded at the claret locus in Drosophila is required for normal chromosome segregation in meiosis in females and in early mitotic divisions of the embryo. Here we show that the predicted amino-acid sequence of this product is related to the heavy chain of kinesin. The conserved region corresponds to the kinesin motor domain and includes the ATP-binding site and a region that can bind microtubules. A second region contains a leucine repeat motif which may mediate protein-subunit interactions necessary for attachment of chromosomes to the spindle. The mutant phenotype of chromosome nondisjunction and loss, and its similarity to the kinesin ATP-binding domain, suggest that the product encoded at claret not only stabilizes chromosome attachments to the spindle, but may also be a motor that drives chromosome segregation in female meiosis.
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PMID:Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin. 213 98

The centrifugal elongation of membranes to form extended tubular structures is a widespread form of intracellular organelle movement. Tubular lysosomes and the endoplasmic reticulum, for example, undergo such extension in association with microtubules, and this process has been mimicked in vitro by combining purified microtubules with isolated membranes and the mechanochemical ATPase kinesin. This, along with evidence that kinesin is associated with the endoplasmic reticulum, has led to the suggestion that kinesin provides the motive force for the formation and maintenance of elongated tubulovesicular structures in cells. We have addressed this hypothesis in murine macrophages, which have prominent tubular lysosomes whose form depends on the integrity of microtubules. Here we report that two antikinesin antibodies which disrupt in vitro motility will each cause centripetal collapse of the array of tubular lysosomes when scrape-loaded into macrophages. To our knowledge this provides the first in vivo evidence that kinesin is responsible for extension of tubulovesicular structures along microtubules.
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PMID:Radial extension of macrophage tubular lysosomes supported by kinesin. 169 3

unc-104 encodes a novel kinesin paralog that may act as a microtubule-based motor in the nervous system. Neuronal cell lineages and axonogenesis are normal in unc-104 null mutants, but axons have few synaptic vesicles and make only a few small synapses. By contrast, neuron cell bodies have surfeits of similar vesicles tethered together within the cytoplasm. Based on behavioral and cellular phenotypes, we suggest that UNC-104 is a neuron-specific motor used for anterograde translocation of synaptic vesicles along axonal microtubules. Other membrane-bounded organelles are transported normally.
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PMID:Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. 171 Jan 72

Biochemical, pharmacological and immunocytochemical studies have implicated the microtubule-activated ATPase, kinesin, in the movement of membrane bounded organelles in fast axonal transport. In vitro studies suggested that kinesin moves organelles preferentially in the anterograde direction, but data about the function and precise localization of kinesin in the living axon were lacking. The current study was undertaken to establish whether kinesin associates with anterograde or retrograde moving organelles in vivo. Peripheral nerves were ligated to produce accumulations of organelles moving in defined directions. Regions proximal (anterograde) and distal (retrograde) to the ligation were analyzed for kinesin localization by immunofluorescence, and by immunogold electron microscopy using ultracryomicrotomy. Substantial amounts of kinesin were associated with anterograde moving organelles on the proximal side, while significantly less kinesin was detected distally. Statistical analyses indicated that kinesin was mostly associated with membrane-bounded organelles. These observations indicate that axonal kinesin is primarily associated with anterograde moving organelles in vivo.
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PMID:Kinesin associates with anterogradely transported membranous organelles in vivo. 171 89

During the first cell cycle, the vegetal cortex of the fertilized frog egg is translocated over the cytoplasm. This process of cortical rotation creates regional cytoplasmic differences important in later development, and appears to involve an array of aligned microtubules that forms transiently beneath the vegetal cortex. We have investigated how these microtubules might be involved in generating movement by analyzing isolated cortices and sections of Xenopus laevis and Rana pipiens eggs. First, the polarity of the cortical microtubules was determined using the "hook" assay. Almost all microtubules had their plus ends pointing in the direction of cortical rotation. Secondly, the association of microtubules with other cytoplasmic elements was examined. Immunofluorescence revealed that cytokeratin filaments coalign with the microtubules. The timing of their appearance and their position on the cytoplasmic side of the microtubules suggested that they are not involved directly in generating movement. ER was visualized with the dye DiIC16(3) and by immunofluorescence with anti-BiP (Bole, D. G., L. M. Hendershot, and J. F. Kearney, 1986. J. Cell Biol. 102:1558-1566). One layer of ER was found closely underlying the plasma membrane at all times. An additional, deeper layer formed in association with the microtubules of the array. Antibodies to sea urchin kinesin (Ingold, A. L., S. A. Cohn, and J. M. Scholey. 1988. J. Cell Biol. 107:2657-2667) detected antigens associated with both the ER and microtubules. On immunoblots they recognized microtubule associated polypeptide(s) of approximately 115 kD from Xenopus eggs. These observations are consistent with a role for kinesin in creating movement between the microtubules and ER, which leads in turn to the cortical rotation.
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PMID:Evidence for the involvement of microtubules, ER, and kinesin in the cortical rotation of fertilized frog eggs. 171 12

Monoclonal antibodies to the axonal transport ATPase kinesin were used in an immunofluorescent study on mammalian nerves. Following crushing of the sciatic nerve and the ventral roots of adult rats, immunoreactive material was found to accumulate rapidly, mainly proximal to a crush but also, to some degree, distal to a crush. The strongest immunofluorescence was observed after incubation with the H2 antibody against the heavy subunit of kinesin. Using the cytofluorimetric scanning (CFS) procedure, the accumulated amounts were quantified and it was found that the retrogradely accumulating kinesin-like immunoreactivity (IR) was about 4-12% of the anterogradely transported kinesin-IR. The results were compared to the vesicle marker p38 (synaptophysin), which was found to accumulate to a significant extent on both sides of the crush. Cytofluorimetric scanning measurements indicated that nearly 50% of the anterogradely accumulated p38-IR was recycling to the cell body. The results demonstrate that kinesin in the living axon is affiliated with anterogradely transported organelles. Retrogradely transported organelles appeared to carry very little kinesin-IR, suggesting that kinesin may be subject to turnover, distinct from that of p38, in the distal regions of the axon.
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PMID:The axonal transport motor 'kinesin' is bound to anterogradely transported organelles: quantitative cytofluorimetric studies of fast axonal transport in the rat. 171 8

Individual microtubules can be visualised by confocal microscopy in reflection mode; when associated with a glass surface, they show up as black lines against the bright reflection from the surface. The high contrast imaging allows details of the behaviour of sliding microtubules to be studied easily. Taxol-stabilised microtubules sliding over kinesin-coated surfaces are normally straight, but can bend into tight loops if the leading end sticks to the surface. Some remain curved after release and move in circles. In such cases, the microtubule lattice must have become stably deformed. Electron microscopy of microtubules fixed during sliding shows no gross rearrangement of the subunit lattice and indicates that microtubule bending is mainly achieved by increased twisting of the longitudinal protofilaments around the microtubule.
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PMID:The bending of sliding microtubules imaged by confocal light microscopy and negative stain electron microscopy. 171 72

In this report we describe the different forms of motile behavior of individual native microtubules from squid giant axons. The three major types of motile behavior of native microtubules are gliding, fishtailing and circling. Gliding, the type of movement observed most often, is the straight translocation of an unbent microtubule segment. Gliding velocities observed in the population ranged from 0.2 to 0.7 microns/s with an average velocity of 0.45 microns/s. The direction of gliding was random with respect to the surface suggesting that physical features of the surface did not influence the direction of gliding. Microtubules are able to glide over objects on the surface and over each other without changing velocity or direction. These observations prove that gliding can continue under conditions where direct contact of the microtubule with the glass surface is not possible along its entire length. When a frontal segment of a microtubule becomes slowed down or attached to the surface, the microtubule begins to fishtail, a process whereby bends form in the frontal part and propagate rearward. The shapes of a fishtailing microtubule resemble that of a beating flagellum. Microtubules with focal attachment near the tip do not propagate bending waves but assume a spiral or circular shape and rotate horizontally (circling). The frontal end of these microtubules stays or rotates in place as pushing forces from the rear turn the microtubule in a circular pattern. An analysis of these data shows that all forms of motion can be explained by pushing forces due to kinesin acting along the length of the microtubule. In an attempt to transport the kinesin-covered cover glass as if it were a big organelle, microtubules translocate themselves in the opposite direction. We estimated the minimum density of force generating enzymes on the surfaces of our preparations as well as that required to maintain active gliding of microtubules. We concluded that the heads of the surface-bound kinesin molecules must display extreme rotatory freedom in order to explain the observed smoothness and straightness of microtubule motion. Few, but usually at least two molecules of kinesin have to work simultaneously to generate the forms of motility observed.
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PMID:Analysis of the gliding, fishtailing and circling motions of native microtubules. 172 29


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