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)

To study the mechanisms that control epithelial commitment and differentiation we have used undifferentiated HT-29 colon cancer cells and a subpopulation of mucus secreting cells obtained by selection of HT-29 cells in 10-6 M methotrexate (M6 cells) as experimental models. We isolated cDNAs encoding transcripts overexpressed in early confluent M6 cells regarding steady-state levels in HT-29 cells by subtractive hybridisation. Fifty-one cDNA clones, corresponding to 34 independent transcripts, were isolated, partially sequenced by their 5' end, and classified into four groups according to their identity: transcripts that included a repeated sequence of the Alu family (10 clones, among them those encoding ribonucleoprotein RNP-L and E-cadherin), transcripts encoded by the mitochondrial genome (nine clones), transcripts encoding components of the protein synthesis machinery (23 clones, including the human ribosomal protein L38 not previously cloned in humans) and nine additional cDNAs that could not be classified in the previous groups. These last included ferritin, cytokeratin 18, translationally controlled human tumour protein (TCHTP), mt-aldehyde dehydrogenase, as well as unknown transcripts (three clones), and the human homologues of the molecular motor kinesin KIF3B and of the ser/thr protein kinase EMK1. Spot dot and Northern blot analyses showed that ser/thr protein kinase EMK1 was differentially expressed in M6 cells when compared with parental HT-29 cells. Steady-state levels of EMK1 were higher in proliferating, preconfluent, M6 and HT-29 cells than in 2 days post confluence (dpc) and 8dpc M6 and HT-29 cells. Transcripts that included an Alu repeat were also shown to be differentially expressed and accumulated in differentiating M6 cells when analysed by Northern blot. The significance of the transcripts cloned is discussed in the context of the commitment and differentiation of the M6 cells to the mucus secreting lineage of epithelial cells.
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PMID:Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements. 1039 37

Cadherin-mediated cell-cell adhesion is a dynamic process that is regulated during embryonic development, cell migration, and differentiation. Different cadherins are expressed in specific tissues consistent with their roles in cell type recognition. In this study, we examine the formation of N-cadherin-dependent cell-cell contacts in fibroblasts and myoblasts. In contrast to E-cadherin, both endogenous and ectopically expressed N-cadherin shuttles between an intracellular and a plasma membrane pool. Initial formation of N-cadherin-dependent cell-cell contacts results from the recruitment of the intracellular pool of N-cadherin to the plasma membrane. N-cadherin also localizes to the Golgi apparatus and both secretory and endocytotic vesicles. We demonstrate that the intracellular pool of N-cadherin is tightly associated with the microtubule (MT) network and that junction formation requires MTs. In addition, localization of N-cadherin to the cortex is dependent on an intact F-actin cytoskeleton. We show that N-cadherin transport requires the MT network as well as the activity of the MT-associated motor kinesin. In conclusion, we propose that N-cadherin distribution is a regulated process promoted by cell-cell contact formation, which controls the biogenesis and turnover of the junctions through the MT network.
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PMID:Biogenesis of N-cadherin-dependent cell-cell contacts in living fibroblasts is a microtubule-dependent kinesin-driven mechanism. 1180 40

p120-catenin exists in a membrane-associated cadherin-bound pool, a cytosolic pool that affects Rho GTPases, and a nuclear pool that is thought to associate with the methylation-relevant transcriptional repressor Kaiso. We show here that cytoplasmic p120 can also associate both directly and indirectly with the microtubule network, and that p120 traffics along microtubules toward their plus ends. The direct binding required most of the armadillo repeats and was mutually exclusive for interaction with E-cadherin. Perturbing the p120-microtubule interaction with nocodazole or taxol markedly affected both the tubulin interaction and the balance between cytoplasmic and nuclear p120. The indirect binding occurred via a novel interaction between a segment of the p120 N-terminal domain and conventional kinesin heavy chains. Selective uncoupling of the p120-kinesin interaction by overexpression of the respective p120 and kinesin-binding fragments promoted nuclear p120 accumulation. In addition, expression of full-length kinesin reduced the nuclear accumulation of p120 and blocked the branching phenotype associated with p120 overexpression. Taken together, the data suggest that kinesin affects both the targeting and activity of p120 at several cellular locations.
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PMID:A novel interaction between kinesin and p120 modulates p120 localization and function. 1467 16

The adherens junction (AJ) plays a crucial role in maintaining cell-cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end-directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin. This cleavage depends on the E3 ubiquitin protein ligase Hakai and is inhibited by proteasome inhibitors. E-cadherin ubiquitination consistently increases after depletion of KIFC3 or USP47. These findings suggest that KIFC3 suppresses the ubiquitination and resultant degradation of E-cadherin by recruiting USP47 to AJs, a process that may be involved in maintaining stable cell-cell adhesion in epithelial sheets.
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PMID:Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions. 2525 21

F-BAR proteins are prime candidates to regulate membrane curvature and dynamics during different developmental processes. Here, we analyzed nostrin, a so-far-unknown Drosophila melanogaster F-BAR protein related to Cip4. Genetic analyses revealed a strong synergism between nostrin and cip4 functions.Whereas single mutant flies are viable and fertile, combined loss of nostrin and cip4 results in reduced viability and fertility. Double mutant escaper flies show enhanced wing polarization defects and females exhibit strong egg chamber encapsulation defects. Live imaging analysis suggests that the observed phenotypes are caused by an impaired turnover of E-cadherin at the membrane. Simultaneous knockdown of Cip4 and Nostrin strongly increases the formation of tubular E-cadherin vesicles at adherens junctions. Cip4 and Nostrin localize at distinct membrane subdomains. Both proteins prefer similar membrane curvatures but seem to form distinct membrane coats and do not heterooligomerize. Our data suggest an important synergistic function of both F-BAR proteins in membrane dynamics. We propose a cooperative recruitment model, in which Cip4 initially promotes membrane invagination and early-actin-based endosomal motility, and Nostrin makes contacts with microtubules through the kinesin Khc-73 for trafficking of recycling endosomes.
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PMID:Cooperative functions of the two F-BAR proteins Cip4 and Nostrin in the regulation of E-cadherin in epithelial morphogenesis. 2582 14

The kinesin KIF17 localizes at microtubule plus-ends where it contributes to regulation of microtubule stabilization and epithelial polarization. We now show that KIF17 localizes at cell-cell adhesions and that KIF17 depletion inhibits accumulation of actin at the apical pole of cells grown in 3D organotypic cultures and alters the distribution of actin and E-cadherin in cells cultured in 2D on solid supports. Overexpression of full-length KIF17 constructs or truncation mutants containing the N-terminal motor domain resulted in accumulation of newly incorporated GFP-actin into junctional actin foci, cleared E-cadherin from cytoplasmic vesicles and stabilized cell-cell adhesions to challenge with calcium depletion. Expression of these KIF17 constructs also increased cellular levels of active RhoA, whereas active RhoA was diminished in KIF17-depleted cells. Inhibition of RhoA or its effector ROCK, or expression of LIMK1 kinase-dead or activated cofilin(S3A) inhibited KIF17-induced junctional actin accumulation. Interestingly, KIF17 activity toward actin depends on the motor domain but is independent of microtubule binding. Together, these data show that KIF17 can modify RhoA-GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells.
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PMID:KIF17 regulates RhoA-dependent actin remodeling at epithelial cell-cell adhesions. 2675 74