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)

Intracellular movement of vesiculated pigment granules in angelfish melanophores is regulated by a signalling pathway that triggers kinesin and dyneinlike microtubule motor proteins. We have tested the relative importance of intracellular Ca2+ ([Ca2+]i) vs cAMP ([cAMP]i) in the control of such motility by adrenergic agonists, using fluorescence ratio imaging and many ways to artificially stimulate or suppress signals in these pathways. Fura-2 imaging reported a [Ca2+]i elevation accompanying pigment aggregation, but this increase was not essential since movement was not induced with the calcium ionophore, ionomycin, nor was movement blocked when the increases were suppressed by withdrawal of extracellular Ca2+ or loading of intracellular BAPTA. The phosphatase inhibitor, okadaic acid, blocked aggregation and induced dispersion at concentrations that suggested that the protein phosphatase PP-1 or PP-2A was continuously turning phosphate over during intracellular motility. cAMP was monitored dynamically in single living cells by microinjecting cAMP-dependent kinase in which the catalytic and regulatory subunits were labeled with fluorescein and rhodamine respectively (Adams et al., 1991. Nature (Lond.). 349:694-697). Ratio imaging of F1CRhR showed that the alpha 2-adrenergic receptor-mediated aggregation was accompanied by a dose-dependent decrease in [cAMP]i. The decrease in [cAMP]i was both necessary and sufficient for aggregation, since cAMP analogs or microinjected free catalytic subunit of A kinase-blocked aggregation or caused dispersal, whereas the cAMP antagonist RpcAMPs or the microinjection of the specific kinase inhibitor PKI5-24 amide induced aggregation. Our conclusion that cAMP, not calcium, controls bidirectional microtubule dependent motility in melanophores might be relevant to other instances of non-muscle cell motility.
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PMID:Intracellular cyclic AMP not calcium, determines the direction of vesicle movement in melanophores: direct measurement by fluorescence ratio imaging. 134 51

Ultrastructural and functional studies of degranulation responses by human neutrophils have suggested that microtubules (MTs) have a role in the intracellular transport of neutrophil granules. We have found that granule-MT complexes can be isolated from disrupted taxol-treated (1.0 microM) neutrophils, visualized by electron microscopy, and quantified in terms of granules per MT length. After incubation of neutrophils with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), granule-MT complex formation was found to be increased two- to threefold. Enhanced binding of granules to MTs was detectable within 30 s of fMLP stimulation and was dependent on the concentration of fMLP. Incubation of cells with dibutyryl cAMP inhibited this fMLP-stimulated granule-MT complex formation in a dose-responsive fashion. These granule-MT interactions could be reproduced in a cell-free system with neutrophil granules isolated by density gradient centrifugation and MTs polymerized from phosphocellulose-purified tubulin. Furthermore, reconstituted granule-MT interactions were found to be modulated by ATPase inhibitors. Sodium orthovanadate increased granule-MT interactions in a concentration-dependent manner, while AMP-PNP, a nonhydrolyzable ATP analogue, and N-ethylmaleimide decreased or eliminated these interactions. In addition, we found that a MT-activated ATPase could be recovered from intact neutrophil granules by salt extraction, and that extracts enriched in this ATPase contained a polypeptide of between 115 and 120 kD which binds ATP and is immunologically related to kinesin. These studies demonstrate that cytoplasmic granules interact with MTs in human neutrophils in a regulated stimulus-responsive manner, and they suggest that such interactions may involve an MT-based, ATPase-dependent, vesicle translocation system as has been demonstrated in other types of cells.
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PMID:Interactions of cytoplasmic granules with microtubules in human neutrophils. 254 7

Kinesin is an ubiquitous heterotetrameric microtubule-based motor which translocates membrane-bound organelles. Since organelle motility and motor protein function can be regulated by components of signaling pathways, the ability of purified bovine brain kinesin (kinesin) to be phosphorylated and to recognize calmodulin (CaM) was tested. Extensively purified "kinesin" was found to consist of several forms of both heavy (KHC) and light (KLC) chains. Phosphorylation of kinesin by a variety of protein kinases was examined; cAMP-dependent protein kinase (cAMP-PK) was the most active enzyme leading to the incorporation of up to 8 mol P/mol kinesin. Phosphorylation occurred predominantly on the KLCs and led to substantial acidic pI shifts. Peptide maps indicated that multiple phosphorylation sites exist on each KLC. Incubation of kinesin in vitro with protein kinase C (PKC) led to the phosphorylation of both KHCs and KLCs. In vivo phosphorylation of KHC and KLCs was demonstrated by immunoprecipitation of [32P]-labeled kinesin from cultured rat hippocampal pyramidal neurons; kinesin phosphorylation was stimulated by 8-chlorophenyl-thio-cAMP or 12-O-tetradecanoylphorbol-13-acetate. Native bovine brain kinesin was shown to bind 125I-CaM by nucleotide-dependent pelleting with stable microtubules. Specific calcium-dependent binding of 125I-CaM to KLCs but not KHC was found using a ligand blotting assay. cAMP-PK phosphorylated kinesin bound 125I-CaM less well than untreated protein in both ligand blotting and microtubule-pelleting paradigms. Calcium-dependent binding of CaM to kinesin inhibited the ATPase activity of native kinesin but not of cAMP-PK phosphorylated kinesin. These results suggest that the KLCs have a regulatory function and integrate information coming from diverse signaling pathways to modulate the activity and function of kinesin.
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PMID:Calmodulin binding to and cAMP-dependent phosphorylation of kinesin light chains modulate kinesin ATPase activity. 838 85

Kinesin is a microtubule-based motor protein involved in intracellular organelle transport. Neurons are characterized by the presence of at least two isoforms of conventional kinesin: ubiquitous kinesin, expressed in all cells and tissues, and neuronal kinesin, whose pattern of expression is confined to neuronal cells. In order to investigate whether the two kinesin motors, which are encoded by different genes, may play distinct biological roles in neurons, we studied their expression during neuronal differentiation. Human neuroblastoma SH-SY5Y and IMR32 cells and rat phaeochromocytoma PC12 cells were used as an in vitro system for neuronal differentiation and were induced to differentiate in the presence of retinoic acid, a combination of dibutyryl cAMP and 5-bromodeoxyuridine, and nerve growth factor respectively. The expression level of each kinesin isoform was evaluated by quantitative immunoblot before and after pharmacological treatment. We found that in all cell types the expression level of neuronal kinesin, but not of ubiquitous kinesin, is stimulated during differentiation. In particular, SH-SY5Y cells show a 4.5-fold, IMR32 cells a 3-fold and PC12 cells a 7-fold increase in the level of expression of neuronal kinesin. By Northern blot analysis we found that the selective increase in the expression of neuronal kinesin is paralleled by an increase in its mRNA, indicating that there is a transcriptional control of the expression of this kinesin isoform during differentiation of neuroblastoma and PC12 cells. Our results suggest that these cells represent an adequate model to study the function of conventional kinesin and its isoforms.
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PMID:Differential expression of ubiquitous and neuronal kinesin heavy chains during differentiation of human neuroblastoma and PC12 cells. 896 45

Microtubules in the axon are uniformly oriented, while microtubules in the dendrite are nonuniformly oriented. We have proposed that these distinct microtubule polarity patterns may arise from a redistribution of molecular motor proteins previously used for mitosis of the developing neuroblast. To address this issue, we performed studies on neuroblastoma cells that undergo mitosis but also generate short processes during interphase. Some of these processes are similar to axons with regard to their morphology and microtubule polarity pattern, while others are similar to dendrites. Treatment with cAMP or retinoic acid inhibits cell division, with the former promoting the development of the axon-like processes and the latter promoting the development of the dendrite-like processes. During mitosis, the kinesin-related motor termed CHO1/MKLP1 is localized within the spindle midzone where it is thought to transport microtubules of opposite orientation relative to one another. During process formation, CHO1/ MKLP1 becomes concentrated within the dendrite-like processes but is excluded from the axon-like processes. The levels of CHO1/MKLP1 increase in the presence of retinoic acid but decrease in the presence of cAMP, consistent with a role for the protein in dendritic differentiation. Moreover, treatment of the cultures with antisense oligonucleotides to CHO1/MKLP1 compromises the formation of the dendrite-like processes. We speculate that a redistribution of CHO1/MKLP1 is required for the formation of dendrite-like processes, presumably by establishing their characteristic nonuniform microtubule polarity pattern.
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PMID:Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells. 902 95

This study investigated regulation of uniform positioning of melanosomes and erythrosomes in chromatophores from spotted triplefin Grahamina capito from New Zealand, by modulating levels of intracellular cAMP. Elevated cAMP levels, caused by forskolin treatment, inhibited aggregation and induced rapid dispersion of melanosomes and erythrosomes. The dispersing organelles moved to and accumulated at the cell periphery, leading to an abnormal hyperdispersed state with a melanosome- or erythrosome-depleted cell center. Minutes after hyperdispersion, these organelles reversed direction and moved towards the center again to finally distribute throughout the cells. When chromatophores with initially dispersed melanosomes or erythrosomes were treated with forskolin, no hyperdispersion was seen, but the erythrosomes aggregated slowly. Disassembly of actin by latrunculin resulted in a similar but constant hyperdispersed melanosome and erythrosome distribution. The results show that cAMP not only disperses but also aggregates melanosomes and erythrosomes, and that it is the intracellular position of these organelles that determine the directionality of the cAMP-induced movement. To ascertain the even distribution in the dispersed state, regulatory components associated with the actin cytoskeleton in the cell periphery might modify activity of cytoplasmic dynein or kinesin upon contact with dispersing melanosomes or erythrosomes.
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PMID:Melanosome and erythrosome positioning regulates cAMP-induced movement in chromatophores from spotted triplefin, Grahamina capito. 1090 Apr 39

The assembly and maintenance of eucaryotic flagella and cilia depend on the microtubule motor, kinesin-II. This plus end-directed motor carries intraflagellar transport particles from the base to the tip of the organelle, where structural components of the axoneme are assembled. Here we test the idea that kinesin-II also is essential for signal transduction. When mating-type plus (mt+) and mating-type minus (mt-) gametes of the unicellular green alga Chlamydomonas are mixed together, binding interactions between mt+ and mt- flagellar adhesion molecules, the agglutinins, initiate a signaling pathway that leads to increases in intracellular cAMP, gamete activation, and zygote formation. A critical question in Chlamydomonas fertilization has been how agglutinin interactions are coupled to increases in intracellular cAMP. Recently, fla10 gametes with a temperature-sensitive defect in FLA10 kinesin-II were found to not form zygotes at the restrictive temperature (32 degrees C). We found that, although the rates and extents of flagellar adhesion in fla10 gametes at 32 degrees C are indistinguishable from wild-type gametes, the cells do not undergo gamete activation. On the other hand, fla10 gametes at 32 degrees C regulated agglutinin location and underwent gamete fusion when the cells were incubated in dibutyryl cAMP, indicating that their capacity to respond to the cAMP signal was intact. We show that the cellular defect in the fla10 gametes at 32 degrees C is a failure to undergo increases in cAMP during flagella adhesion. Thus, in addition to being essential for assembly and maintenance of the structural components of flagella, kinesin-II/intraflagellar transport plays a role in sensory transduction in these organelles.
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PMID:Kinesin-II is required for flagellar sensory transduction during fertilization in Chlamydomonas. 1195 Sep 49

In fish melanophores, melanosomes can either aggregate around the cell centre or disperse uniformly throughout the cell. This organelle transport involves microtubule- and actin-dependent motors and is regulated by extracellular stimuli that modulate levels of intracellular cyclic adenosine 3-phosphate (cAMP). We analysed melanosome dynamics in Atlantic cod melanophores under different experimental conditions in order to increase the understanding of the regulation and relative contribution of the transport systems involved. By inhibiting dynein function via injection of inhibitory antidynein IgGs, and modulating cAMP levels using forskolin, we present cellular evidence that dynein is inactivated by increased cAMP during dispersion and that the kinesin-related motor is inactivated by low cAMP levels during aggregation. Inhibition of dynein further resulted in hyperdispersed melanosomes, which subsequently reversed movement towards a more normal dispersed state, pointing towards a peripheral feedback regulation in maintaining the evenly dispersed state. This reversal was blocked by noradrenaline. Analysis of actin-mediated melanosome movements shows that actin suppresses aggregation and dispersion, and indicates the possibility of down-regulating actin-dependent melanosome movement by noradrenaline. Data from immuno-electron microscopy indicate that myosinV is associated with fish melanosomes. Taken together, our study presents evidence that points towards a model where both microtubule- and actin-mediated melanosome transport are synchronously regulated during aggregation and dispersion, and this provides a cell physiological explanation behind the exceptionally fast rate of background adaptation in fish.
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PMID:Regulatory control of both microtubule- and actin-dependent fish melanosome movement. 1221 92

Melanophore melanosomes organelles can be regulated to move and locate correspondingly to many other different organelle types. Comparing lessons from analysis of a specific melanosome distribution can, therefore, contribute to the understanding of distribution of other organelles, and vice versa. From such data, it is now generally accepted that microtubules provide directed long-distance movement, while cell peripheral movements include microfilaments. In fish melanophores, both actin and dynein exhibit counter-forces to the kinesin-like protein in maintaining the evenly dispersed state, while actin and kinesin exhibit counter-forces to dynein in many other systems. Lessons from elevating cAMP levels indicate the presence of a peripheral feedback regulatory system involved in maintaining the evenly dispersed state. Studies from dynein inhibition suggest that the kinesin-like protein involved in fish melanosome dispersal is regulated in contrast to many other systems. One would further expect melanosome transport to be regulated also on actin/myosin, in order to prevent actin-dependent capture of melanosomes during the microtubule-dependent aggregation and dispersion. General findings will be discussed in comparison with positioning and movement of other organelle types in cells. Finally, recent data on melanosome-dependent organising of microtubules show that dynein is involved in nucleating microtubules extending from melanosome aggregates in melanophore fragments.
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PMID:The cytoskeleton in fish melanophore melanosome positioning. 1224 3

The kinesin superfamily proteins (KIFs) play essential roles in receptor transportation along the microtubules. KIF17 transports the N-methyl-d-aspartate receptor NR2B subunit in vitro, but its role in vivo is unknown. To clarify this role, we generated transgenic mice overexpressing KIF17 tagged with GFP. The KIF17 transgenic mice exhibited enhanced learning and memory in a series of behavioral tasks, up-regulated NR2B expression with the potential involvement of a transcriptional factor, the cAMP-dependent response element-binding protein, and increased phosphorylation of the cAMP-dependent response element-binding protein. Our results suggest that the motor protein KIF17 contributes to neuronal events required for learning and memory by trafficking fundamental N-methyl-d-aspartate-type glutamate receptors.
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PMID:Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. 1239 Dec 94


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