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)

We examined cytoskeleton-associated forms of NF proteins during axonal neuritogenesis in cultured dorsal root ganglion (DRG) neurons and NB2a/d1 neuroblastoma. In addition to filamentous immunoreactivity, we observed punctate NF immunoreactivity throughout perikarya and neurites. Immuno-electron microscopy revealed this punctate immunoreactivity to consist of non-membrane-bound 75 nm round/ovoid structures consisting of amorphous, fibrous material. Endogenous and microinjected NF subunits incorporated into dots prior to their accumulation within filaments. A transfected GFP-conjugated NF-M incorporated into dots and translocated at a rate consistent with slow axonal transport in real-time video analyses. Some dots converted into a filamentous form or exuded filamentous material during transport. Dots contained conventional kinesin immunoreactivity, associated with microtubules, and their transport into axons was blocked by anti-kinesin antibodies and nocodazole. These oligomeric structures apparently represent one form in which NF subunits are transported in growing axons and may utilize kinesin as a transport motor.
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PMID:Kinesin-mediated transport of neurofilament protein oligomers in growing axons. 1052 15

KLP64D and KLP68D are members of the kinesin-II family of proteins in Drosophila. Immunostaining for KLP68D and ribonucleic acid in situ hybridization for KLP64D demonstrated their preferential expression in cholinergic neurons. KLP68D was also found to accumulate in cholinergic neurons in axonal obstructions caused by the loss of kinesin light chain. Mutations in the KLP64D gene cause uncoordinated sluggish movement and death, and reduce transport of choline acetyltransferase from cell bodies to the synapse. The inviability of KLP64D mutations can be rescued by expression of mammalian KIF3A. Together, these data suggest that kinesin-II is required for the axonal transport of a soluble enzyme, choline acetyltransferase, in a specific subset of neurons in Drosophila. Furthermore, the data lead to the conclusion that the cargo transport requirements of different classes of neurons may lead to upregulation of specific pathways of axonal transport.
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PMID:Kinesin-II is required for axonal transport of choline acetyltransferase in Drosophila. 1054 96

In axons, organelles move away from (anterograde) and toward (retrograde) the cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast axonal transport. It is reasonable to expect that cytoplasmic dynein is a fast retrograde motor, but relatively few tests of dynein function have been reported with neurons of intact organisms. In extruded axoplasm, antibody disruption of kinesin or the dynactin complex (a dynein activator) inhibits both retrograde and anterograde transport. We have tested the functions of the cytoplasmic dynein heavy chain (cDhc64C) and the p150(Glued) (Glued) component of the dynactin complex with the use of genetic techniques in Drosophila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal swellings filled with retrograde and anterograde cargoes, were similar to those caused by kinesin mutations. Why do specific disruptions of unidirectional motor systems cause bidirectional defects? Direct protein interactions of kinesin with dynein heavy chain and p150(Glued) were not detected. However, strong dominant genetic interactions between kinesin, dynein, and dynactin complex mutations in axonal transport were observed. The genetic interactions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidirectional disruption phenotypes and the dominant genetic interactions demonstrate that cytoplasmic dynein, the dynactin complex, and conventional kinesin are interdependent in fast axonal transport.
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PMID:Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport. 1056 67

The distribution of the major cytoskeletal components in frontal cryosections of the hippocampal formation of adult male tree shrews (Tupaia belangeri) was immunohistochemically investigated by using commercially available antibodies. Actin-immunolabeling was evident in all layers of the dentate gyrus as well as in the regio superior (CA1) and the regio inferior (CA3). Neurofilament 160 was detected only in the molecular layer of the dentate gyrus and in the axons of the granule cells (mossy fibers). For beta-tubulin, the microtubule associated proteins (MAPs) MAP2AB, MAP2ABC and Tau, immunoreactivity was evident within the granule cells and within the somatodendritic compartment of pyramidal neurons. Granule cells and the somata of the pyramidal neurons were intensely labeled for kinesin. Our findings show the elaborate expression of cytoskeletal proteins in the hippocampal formation of the tree shrew, relatively similar to what is seen in other species but with also some important differences, such as the immunonegativity of the axonal compartment for Tau in the tree shrew, which is contrary to what we see in the mouse (unpublished data). These findings provide useful insights regarding the organization of the hippocampal formation of the tree shrew and are fundamental for further research in this field.
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PMID:Mapping of cytoskeletal components in the hippocampal formation of the tree shrew (Tupaia belangeri). 1058 59

The molecular motors dynein and kinesin are large protein complexes that convert the energy generated by ATP hydrolysis into directional movement along the microtubule cytoskeleton. They are required for a myriad of cellular processes, including mitotic spindle movement, axonal and vesicular transport, and ciliary beating. Recently, it has been shown that, in addition, they have a unique role during embryonic patterning: they are required to orient and establish the left-right axis in early vertebrate development.
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PMID:Molecular motors: the driving force behind mammalian left-right development. 1065 13

Exposure to occupational and environmental toxicants can result in distal axonopathies through reaction with various components of the axonal cytoskeleton. The solvents n-hexane and methyl n-butyl ketone are metabolized to the beta-diketone, 2,5-hexanedione, which covalently cross-links neurofilaments, resulting in large paranodal axonal swellings filled with neurofilaments. Carbon disulfide exposure leads to an identical axonopathy, achieving neurofilament cross-linking through a parallel series of reactions. Acrylamide and ethylene oxide, on the other hand, adduct proteins but do not lead to cross-linking. These toxicants appear to affect the function of microtubule-associated proteins, such as kinesin, and result in the impaired transport of synaptic vesicles.
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PMID:Neurotoxicants and the cytoskeleton. 1067 57

In neurons, cytoplasmic dynein is synthesized in the cell body, but its function is to move cargo from the axon back to the cell body. Dynein must therefore be delivered to the axon and its motor activity must be regulated during axonal transport. Cytoplasmic dynein is a large protein complex composed of a number of different subunits. The dynein heavy chains contain the motor domains and the intermediate chains are involved in binding the complex to cargo. Five different intermediate chain polypeptides, which are the result of the alternative splicing of the two intermediate chain genes, have been identified. We have characterized two distinct pools of dynein that are transported from the cell body along the axon by different mechanisms. One pool, which contains the ubiquitous intermediate chain, is associated with the membranous organelles transported by kinesin in the fast transport component. The other pool, which contains the other developmentally regulated intermediate chains, is transported in slow component b. The mechanism of dynein regulation will therefore depend on which pool of dynein is recruited to function as the retrograde motor. In addition, the properties of the large pool of dynein associated with actin in slow component b are consistent with the hypothesis that this dynein may be the motor for microtubule transport in the axon.
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PMID:Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons. 1072 78

Recent studies demonstrate co-localization of kinesin with neurofilament (NF) subunits in culture and suggest that kinesin participates in NF subunit distribution. We sought to determine whether kinesin was also associated with NF subunits in situ. Axonal transport of NF subunits in mouse optic nerve was perturbed by the microtubule (MT)-depolymerizing drug vinblastine, indicating that NF transport was dependent upon MT dynamics. Kinesin co-precipitated during immunoprecipitation of NF subunits from optic nerve. The association of NFs and kinesin was regulated by NF phosphorylation, since (1) NF subunits bearing developmentally delayed phospho-epitopes did not co-purify in a microtubule motor preparation from CNS while less phosphorylated forms did; (2) subunits bearing these phospho-epitopes were selectively not co-precipitated with kinesin; and (3) phosphorylation under cell-free conditions diminished the association of NF subunits with kinesin. The nature and extent of this association was further examined by intravitreal injection of (35)S-methionine and monitoring NF subunit transport along optic axons. As previously described by several laboratories, the wave of NF subunits underwent a progressive broadening during continued transport. The front, but not the trail, of this broadening wave of NF subunits was co-precipitated with kinesin, indicating that (1) the fastest-moving NFs were associated with kinesin, and (2) that dissociation from kinesin may foster trailing of NF subunits during continued transport. These data suggest that kinesin participates in NF axonal transport either by directly translocating NFs and/or by linking NFs to transporting MTs. Both Triton-soluble as well as cytoskeleton-associated NF subunits were co-precipitated with kinesin; these data are considered in terms of the form(s) in which NF subunits undergo axonal transport.
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PMID:Phospho-dependent association of neurofilament proteins with kinesin in situ. 1074 58

Null mutations in the Drosophila Kinesin heavy chain gene (Khc), which are lethal during the second larval instar, have shown that conventional kinesin is critical for fast axonal transport in neurons, but its functions elsewhere are uncertain. To test other tissues, single imaginal cells in young larvae were rendered null for Khc by mitotic recombination. Surprisingly, the null cells produced large clones of adult tissue. The rates of cell proliferation were not reduced, indicating that conventional kinesin is not essential for cell growth or division. This suggests that in undifferentiated cells vesicle transport from the Golgi to either the endoplasmic reticulum or the plasma membrane can proceed at normal rates without conventional kinesin. In adult eye clones produced by null founder cells, there were some defects in differentiation that caused mild ultrastructural changes, but they were not consistent with serious problems in the positioning or transport of endoplasmic reticulum, mitochondria, or vesicles. In contrast, defective cuticle deposition by highly elongated Khc null bristle shafts suggests that conventional kinesin is critical for proper secretory vesicle transport in some cell types, particularly ones that must build and maintain long cytoplasmic extensions. The ubiquity and evolutionary conservation of kinesin heavy chain argue for functions in all cells. We suggest interphase organelle movements away from the cell center are driven by multilayered transport mechanisms; that is, individual organelles can use kinesin-related proteins and myosins, as well as conventional kinesin, to move toward the cell periphery. In this case, other motors can compensate for the loss of conventional kinesin except in cells that have extremely long transport tracks.
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PMID:Clonal tests of conventional kinesin function during cell proliferation and differentiation. 1074 33

Cytoplasmic dynein is a motor for retrograde axonal transport for movement of membranous organelles toward the neuronal cell body. However, cytoplasmic dynein is synthesized in the cell body and conveyed along the axon to nerve terminals. To characterize the axonal transport of cytoplasmic dynein in relation to synaptic vesicles and other membrane compartments, immunocytochemical and cytofluorimetric scanning analyses of crush-operated rat sciatic nerves were performed. Distal to the crush, the kinetics of dynein accumulation were consistent with its role in the retrograde transport of membranous organelles. During the initial 3 hr after crush, only small amounts of dynein-immunoreactive material accumulated proximal to the crush. This is consistent with metabolic labeling studies showing that most of the dynein moving in the anterograde direction is in the slow component of axonal transport. Thereafter, the rate of proximal accumulation of dynein increased, and by 8 hr postcrush a large amount of dynein immunoreactivity was observed. This accelerated accumulation may be due to recruitment of dynein from slow component b onto organelles proximal to the crush. Double labeling demonstrated that dynein immunoreactivity colocalized with synaptophysin, a transmembrane protein found in small, clear synaptic vesicles. In contrast, dynein immunoreactivity did not colocalize well with calcitonin gene-related peptide (CGRP), a peptide matrix marker for some large dense-cored vesicles. Finally, dynein immunoreactivity colocalized with the anterograde transport motor kinesin both proximal and distal to a crush, suggesting that kinesin may carry some dynein-containing membrane compartments during fast anterograde axonal transport.
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PMID:Cytoplasmic dynein conversion at a crush injury in rat peripheral axons. 1087 88


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