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)

The interaction of different protein systems with microtubules is a critical step in the cellular function of these organelles. The family of microtube-associated proteins (MAPs) together with a set of motor proteins such as kinesin, cytosolic dynein and dynamin are among the most clear examples of microtubule-interacting proteins. In addition, an increasing number of recently discovered proteins have been shown to interact with microtubules, even though they do not remain associated after cycles of assembly and disassembly. By using affinity columns of agarose derivatized with peptides from the C-terminal regulatory domain on tubulin, we found a 90 kDa protein that interacts with tubulin and microtubules. This protein, here designated as Mip-90, was isolated from neuroblastoma N2A and HeLa cells. It was also identified in high-speed supernatants of the neuroblastoma N-115, and non-neuronal cell lines NIH 3T3, Huh-7, HTB-145 and SW-13 vim+. Mip-90 was able to specifically bind to affinity columns of the agarose-bound beta-II(422-434) and beta-II(434-443) tubulin peptides, containing the sequences of MAP binding domains on beta-II-tubulin. Specific antibodies to Mip-90 along with an anti-beta-tubulin antibody used in double immunofluorescence experiments revealed a striking colocalization of this protein with the microtubule network. Nocodazole-treated cells showed significant changes in Mip-90 distribution as correlated to disruption of the microtubule cytoskeleton. On the other hand, Mip-90 colocalized with microtubule bundles with a perinuclear distribution in HeLa cells treated with taxol. The binding of Mip-90 to microtubules was confirmed by cosedimentation experiments. This protein also exhibited a strong affinity for a calmodulin-agarose affinity matrix, and a preparation of Mip-90 isolated by this affinity procedure was able to promote in vitro tubulin assembly into microtubules. The capacity of Mip-90 to interact with microtubules and with calmodulin suggested functional similarities to tau proteins. However, Western blot analysis using a polyclonal antibody against this protein revealed no cross-reactivity of Mip-90 with tau components. In addition, the 90 kDa protein is a thermosensitive protein. On the other hand, site-directed antibodies that recognize a repetitive binding domain on tau, MAP-2 and MAP-4 failed to react with Mip-90. The studies suggest that Mip-90, a microtubule-interacting protein incorporates into microtubules in vitro, and may play a role in modulating microtubule assembly and organization in non-neuronal cells, thus contributing to the regulation of the dynamics of the cytoskeletal network.
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PMID:Identification of a new microtubule-interacting protein Mip-90. 766 57

Myelin basic protein (MBP) mRNA is localized to the myelin membranes of oligodendrocytes. When exogenous MBP mRNA is microinjected into oligodendrocytes in culture, it is transported along the processes and localized to the myelin compartment in a multistep intracellular RNA trafficking pathway. In the work described here, oligodendrocytes were treated with agents that affect the cytoskeleton including: nocodazole, to disrupt microtubules; taxol, to stabilize microtubules; cytochalasin, to disrupt microfilaments; and kinesin anti-sense oligonucleotide, to suppress kinesin expression. Digoxigenin-labeled MBP mRNA was microinjected into the treated cells and the extent of translocation of the microinjected RNA was determined by confocal microscopy. Nocodazole, taxol, and kinesin anti-sense oligonucleotide inhibited translocation of microinjected MBP mRNA, while cytochalasin B and kinesin sense oligonucleotide did not. These results indicate that translocation of MBP mRNA in oligodendrocytes requires intact microtubules and kinesin but does not require intact microfilaments. The results are discussed in relation to the current multistep model for intracellular RNA trafficking in oligodendrocytes.
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PMID:Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin. 941 74

We have previously documented a novel biphasic traffic pattern for epidermal growth factor (EGF) in the acinar epithelial cell of the lacrimal gland. Different from the typical paradigm observed in many other cell types, EGF initially accumulates in the acinar basal-lateral recycling endosome, then is re-directed to the prelysosomes and lysosomes and degraded. While the cellular content of intact EGF decreases by 40% between 20 and 120 m of continuous incubation at 37 degrees C, the EGF receptor (EGFR) content decreases only modestly [J. Cell Physiol. 199 (2004) 108]. The purpose of the present study was to investigate the role of the microtubule cytoskeleton in this traffic. Primary cultured rabbit lacrimocytes were incubated with [(125)I]-EGF, lysed, and analyzed by subcellular fractionation on sorbitol density gradients. Nocodazole treatment appeared to slightly decrease the initial uptake rate but to have no significant effect on the total amount of [(125)I] accumulation. However, it enhanced accumulation of [(125)I]-EGF and EGFR in the basal-lateral recycling endosome, and it enhanced accumulation of prepro- and pro- cathepsin B in fractions containing late endosomes and prelysosomes. Nocodazole permitted the time-dependent release of [(125)I]-EGF from the recycling endosome, but it partially inhibited [(125)I]-EGF degradation and decreased accumulation of [(125)I]-labeled degradation products in the lysosome. The microtubule-based molecular motors, cytoplasmic dynein and kinesin, were localized in compartments containing the late endosomes, prelysosomes, and lysosomes, consistent with the suggestion that microtubule-based molecular motors play important roles in traffic within the lysosomal pathway. Confocal fluorescence microscopy imaging of FITC-EGF substantiated the effects observed in biochemical studies by demonstrating that nocodazole increased accumulation in a peripheral compartment and decreased traffic to a perinuclear compartment. These data suggest that initial accumulation in the basal-lateral recycling endosome and subsequent release from the recycling endosome to the late endosomes and prelysosome are not microtubule-dependent. On the other hand, microtubule-based motors are more critical for traffic from the prelysosome to the lysosome.
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PMID:Role of the microtubule cytoskeleton in traffic of EGF through the lacrimal acinar cell endomembrane network. 1510 16

Neurofilament (NF) subunits translocate within axons as short NFs, non-filamentous punctate structures ('puncta') and diffuse material that might comprise individual subunits and/or oligomers. Transport of NFs into and along axons is mediated by the microtubule (MT) motor proteins kinesin and dynein. Despite being characterized as a retrograde motor, dynein nevertheless participates in anterograde NF transport through associating with long MTs or the actin cortex through its cargo domain; relatively shorter MTs associated with the motor domain are then propelled in an anterograde direction, along with any linked NFs. Here, we show that inhibition of dynein function, through dynamitin overexpression or intracellular delivery of anti-dynein antibody, selectively reduced delivery of GFP-tagged short NFs into the axonal hillock, with a corresponding increase in the delivery of puncta, suggesting that dynein selectively delivered short NFs into axonal neurites. Nocodazole-mediated depletion of short MTs had the same effect. By contrast, intracellular delivery of anti-kinesin antibody inhibited anterograde transport of short NFs and puncta to an equal extent. These findings suggest that anterograde axonal transport of linear NFs is more dependent upon association with translocating MTs (which are themselves translocated by dynein) than is transport of NF puncta or oligomers.
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PMID:Differential roles of kinesin and dynein in translocation of neurofilaments into axonal neurites. 2136 89

Kif26b, a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. Kif26b expression is restricted to the metanephric mesenchyme, and its transcription is regulated by a zinc finger transcriptional regulator Sall1. However, the mechanism(s) by which Kif26b protein is regulated remain unknown. Here, we demonstrate phosphorylation and subsequent polyubiquitination of Kif26b in the developing kidney. We find that Kif26b interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney. Phosphorylation of Kif26b at Thr-1859 and Ser-1962 by the cyclin-dependent kinases (CDKs) enhances the interaction of Kif26b with Nedd4. Nedd4 polyubiquitinates Kif26b and thereby promotes degradation of Kif26b via the ubiquitin-proteasome pathway. Furthermore, Kif26b lacks ATPase activity but does associate with microtubules. Nocodazole treatment not only disrupts the localization of Kif26b to microtubules but also promotes phosphorylation and polyubiquitination of Kif26b. These results suggest that the function of Kif26b is microtubule-based and that Kif26b degradation in the metanephric mesenchyme via the ubiquitin-proteasome pathway may be important for proper kidney development.
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PMID:Phosphorylation of Kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development. 2276 11