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 role of the microtubule-based motor, kinesin, in membrane trafficking has been investigated in resting and stimulated acinar cells from rabbit lacrimal gland, a cholinergically controlled secretory tissue. Microtubule-dependent motors from extracts of control and carbachol-treated acini were isolated by microtubule-affinity purification and their activity was determined using a video-enhanced differential interference contrast microscopy assay for microtubule gliding. The observation that carbachol treatment resulted in a 2.2-fold stimulation of the frequency of GTP-dependent microtubule gliding in fractions isolated by microtubule-affinity purification and GTP release suggested that kinesin was a target of carbachol-induced stimulation. Resolution of membranes from resting cells by fractionation on a sorbitol density gradient followed by partitioning analysis in a dextran-polyethyleneglycol two-phase system revealed that membrane-associated kinesin codistributed with Golgi-derived membranes, a post-Golgi secretory compartment designated Hex1, membranes from a trans Golgi network-like compartment, endoplasmic reticulum and a group of putative lysosomal membranes containing cathepsin B. Comparable fractionation of carbachol-treated acini showed that stimulation caused redistributions of membrane-associated kinesin, the secretory enzyme beta-hexosaminidase, and galactosyltransferase that appeared to reflect both a reorganization within the Golgi complex and a return of material to the Golgi complex from the secretory pathway. Our findings that carbachol promotes activation of lacrimal acinar kinesin as well as major shifts in kinesin-membrane association within the secretory pathway suggests that kinesin plays a major role in secretory vesicle assembly, apical secretion, and/or secretory vesicle membrane recycling in the lacrimal gland.
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PMID:Cholinergic stimulation of lacrimal acinar cells promotes redistribution of membrane-associated kinesin and the secretory protein, beta-hexosaminidase, and increases kinesin motor activity. 917 47

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

Inositol 1,4,5-trisphosphate (IP3) is a second messenger that induces the release of calcium from the endoplasmic reticulum (ER). The IP3 receptor was discovered as a developmentally regulated glycophosphoprotein, P400, that is absent in strains of mutant mice. The crystal structures of the IP3-binding core and N-terminal suppressor sequence of the IP3 receptor have been identified. The IP3-binding core's affinity to IP3 is similar among the three isoforms of IP3 receptors; however, the N-terminal IP3-binding suppressor region is responsible for isoform-specific IP3-binding affinity tuning. Various pathways for the trafficking of IP3 receptors have been identified; for example, the ER forms a meshwork on which IP3 receptors move by lateral diffusion, and vesicular ER subcompartments containing IP3 receptors move rapidly along microtubules using a kinesin motor. Furthermore, IP3 receptor messenger RNA within messenger RNA granules also moves along microtubules. Recently, we discovered that IP3 receptors play a crucial role in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP3 type 1 receptor activity. IP3 receptor also releases IP3 receptor-binding protein released with IP3 (IRBIT). IRBIT is a pseudoligand for IP3 that regulates the frequency and amplitude of calcium oscillations through the IP3 receptor. IRBIT binds to pancreas-type sodium bicarbonate cotransporter 1, which is important for acid-base balance. Type 2 and 3 double-deficient mice show a deficit in saliva and lacrimal and pancreatic juice secretion. Type 1 IP3 receptor influences brain-derived neurotrophic factor production.
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PMID:The role of Ca2+ signaling in cell function with special reference to exocrine secretion. 1881 72