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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)

Kinesin and cytoplasmic dynein are two major molecular motors responsible for fast axonal transport. As visualized by immunohistochemistry with monoclonal antibodies, both motors were found to be distributed throughout the cell bodies, dendrites and axons of motor neurons in normal human spinal cords. Large axonal swellings, spheroids, in the spinal cords of patients with motor neuron disease showed massive accumulation of kinesin co-localized with highly phosphorylated neurofilaments. Of 114 spheroids in five spinal cords, 87% were stained heavily with the three anti-kinesin antibodies used in this study. Cytoplasmic dynein was scarce or absent in most of the spheroids. These findings suggest that kinesin selectively accumulates in the spheroids of motor neuron axons, causing disturbance of the machinery for anterograde fast axonal transport in motor neuron disease.
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PMID:Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease. 970 Jul 1

It is well established that the microtubules of the mitotic spindle are organized by a variety of motor proteins, and it appears that the same motors or closely related variants organize microtubules in the postmitotic neuron. Specifically, cytoplasmic dynein and the kinesin-related motor known as CHO1/MKLP1 are used within the mitotic spindle, and recent studies suggest that they are also essential for the establishment of the axonal and dendritic microtubule arrays of the neuron. Other motors are required to tightly regulate microtubule behaviors in the mitotic spindle, and it is attractive to speculate that these motors might also help to regulate microtubule behaviors in the neuron. Here we show that a homolog of the mitotic kinesin-related motor known as Eg5 continues to be expressed in rodent neurons well after their terminal mitotic division. In neurons, Eg5 is directly associated with the microtubule array and is enriched within the distal regions of developing processes. This distal enrichment is transient, and typically lost after a process has been clearly defined as an axon or a dendrite. Strong expression can resume later in development, and if so, the protein concentrates within newly forming sprouts at the distal tips of dendrites. We suggest that Eg5 generates forces that help to regulate microtubule behaviors within the distal tips of developing axons and dendrites.
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PMID:Expression of the mitotic motor protein Eg5 in postmitotic neurons: implications for neuronal development. 974 51

Caenorhabditis elegans dynamin is expressed at high levels in neurons and at lower levels in other cell types, consistent with the important role that dynamin plays in the recycling of synaptic vesicles. Indirect immunofluorescence showed that dynamin is concentrated along the dorsal and ventral nerve cords and in the synapse-rich nerve ring. Green fluorescent protein (GFP) fused to the N terminus of dynamin is localized to synapse-rich regions. Furthermore, this chimera was detected along the apical membrane of intestinal cells, in spermathecae, and in coelomocytes. Dynamin localization was not affected by disrupting axonal transport of synaptic vesicles in the unc-104 (kinesin) mutant. To investigate the alternative mechanisms that dynamin might use for translocation to the synapse, we systematically tested the localization of different protein domains by fusion to GFP. Localization of each chimera was measured in one specific neuron, the ALM. The GTPase, a middle domain, and the putative coiled coil each contribute to synaptic localization. Surprisingly, the pleckstrin homology domain and the proline-rich domain, which are known to bind to coated-pit constituents, did not contribute to synaptic localization. The GFP-GTPase chimera was most strongly localized, although the GTPase domain has no known interactions with proteins other than with dynamin itself. Our results suggest that different dynamin domains contribute to axonal transport and the sequestration of a pool of dynamin molecules in synaptic cytosol.
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PMID:Contribution of the GTPase domain to the subcellular localization of dynamin in the nematode Caenorhabditis elegans. 980 8

The neuronal microtubule-associated protein tau plays an important role in establishing cell polarity by stabilizing axonal microtubules that serve as tracks for motor-protein-driven transport processes. To investigate the role of tau in intracellular transport, we studied the effects of tau expression in stably transfected CHO cells and differentiated neuroblastoma N2a cells. Tau causes a change in cell shape, retards cell growth, and dramatically alters the distribution of various organelles, known to be transported via microtubule-dependent motor proteins. Mitochondria fail to be transported to peripheral cell compartments and cluster in the vicinity of the microtubule-organizing center. The endoplasmic reticulum becomes less dense and no longer extends to the cell periphery. In differentiated N2a cells, the overexpression of tau leads to the disappearance of mitochondria from the neurites. These effects are caused by tau's binding to microtubules and slowing down intracellular transport by preferential impairment of plus-end-directed transport mediated by kinesin-like motor proteins. Since in Alzheimer's disease tau protein is elevated and mislocalized, these observations point to a possible cause for the gradual degeneration of neurons.
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PMID:Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease. 981 97

Transgenic mice that express a mutant Cu/Zn superoxide dismutase (SOD1) gene have been provided a valuable model for human amyotrophic lateral sclerosis (ALS). We studied a possible impairment of fast axonal transport in transgenic mice carrying a Gly93-->Ala (G93A) mutant SOD1 gene found in human familial ALS (FALS). Left sciatic nerve was ligated for 6 h in transgenic (Tg) and age-matched wild-type (WT) mice. Immunohistochemical analyses were performed for accumulations of kinesin and cytoplasmic dynein on both sides of the ligation site. Clinical function and histology in the spinal cords, sciatic nerves and gastrocnemius muscles were also assessed. The mice were examined at an early asymptomatic stage (aged 19 weeks) and a late stage (30 weeks) just before the development of the symptoms. WT mice showed an apparent increase in immunoreactivities for kinesin and cytoplasmic dynein at proximal and distal of the ligation, respectively. In contrast, the young Tg mice showed a selective decrease of kinesin accumulation in the proximal of the ligation. The mice were asymptomatic with a mild histological change only in muscles. The old Tg mice showed a marked reduction of the immunoreactivity for kinesin and cytoplasmic dynein on both sides of the ligation. They had a significant loss of spinal motor neurons, relatively small myelinated fiber densities of sciatic nerves, and severe muscular changes. These results provide direct evidence that the SOD1 mutation leads to impaired fast axonal transport, particularly in the anterograde direction at an early, asymptomatic stage preceding loss of spinal motor neurons and peripheral axons. This impairment may contribute to subsequent selective motor neuron death in the present model implicated for human FALS.
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PMID:Selective impairment of fast anterograde axonal transport in the peripheral nerves of asymptomatic transgenic mice with a G93A mutant SOD1 gene. 1008 67

Neurons use kinesin and dynein microtubule-dependent motor proteins to transport essential cellular components along axonal and dendritic microtubules. In a search for new kinesin-like proteins, we identified two neuronally enriched mouse kinesins that provide insight into a unique intracellular kinesin targeting mechanism in neurons. KIF21A and KIF21B share colinear amino acid similarity to each other, but not to any previously identified kinesins outside of the motor domain. Each protein also contains a domain of seven WD-40 repeats, which may be involved in binding to cargoes. Despite the amino acid sequence similarity between KIF21A and KIF21B, these proteins localize differently to dendrites and axons. KIF21A protein is localized throughout neurons, while KIF21B protein is highly enriched in dendrites. The plus end-directed motor activity of KIF21B and its enrichment in dendrites indicate that models suggesting that minus end-directed motor activity is sufficient for dendrite specific motor localization are inadequate. We suggest that a novel kinesin sorting mechanism is used by neurons to localize KIF21B protein to dendrites since its mRNA is restricted to the cell body.
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PMID:Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B. 1022 49

The human ATSV (axonal transporter of synaptic vesicles) gene encodes an anterograde axonal motor transport protein and demonstrates homology to the kinesin gene family in several species. The human ATSV gene was mapped to chromosome 2q37 by screening of a human/rodent somatic cell hybrid panel by the polymerase chain reaction and by fluorescent in situ hybridization analysis using genomic and cDNA clones.
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PMID:Mapping of the kinesin-related gene ATSV to chromosome 2q37. 1032 50

Kinesin and kinesin superfamily proteins are molecular motors involved in important intracellular functions such as organelle transport and cell division. They are microtubule-activated ATPases composed of a motor domain that binds to microtubules and a cargo-binding domain that binds to specific organelles. While searching for the slow Wallerian degeneration mutation (WldS) on distal mouse Chromosome (Chr) 4, we have identified a member of the kinesin superfamily whose predicted gene product has the N-terminal motor domain of Kif1b and a novel C-terminal cargo-binding domain homologous to Kif1a. Kif1b is responsible for the movement of mitochondria along the axon, but the novel isoform containing the alternative C-terminal domain is likely to have a different cargo-binding specificity. cDNA library screening and Northern blot analysis indicate that the alternatively spliced form of Kif1b containing the novel 3'end accounts for the most part of Kif1b expression. We also found more alternatively spliced exons that can give rise to heterogeneous transcripts. Therefore, alternative splicing, as well as multiple genes, may contribute to the selective movement of diverse organelles by anterograde axonal transport. Kif1b maps on distal mouse Chr 4, within the Wld genetic candidate interval, but outside the recently identified triplication. There is, however, no evidence that Kif1b is the Wld gene.
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PMID:The major brain isoform of kif1b lacks the putative mitochondria-binding domain. 1034 Oct 97

Eukaryotic organisms utilize microtubule-dependent motors of the kinesin and dynein superfamilies to generate intracellular movement. To identify new genes involved in the regulation of axonal transport in Drosophila melanogaster, we undertook a screen based upon the sluggish larval phenotype of known motor mutants. One of the mutants identified in this screen, roadblock (robl), exhibits diverse defects in intracellular transport including axonal transport and mitosis. These defects include intra-axonal accumulations of cargoes, severe axonal degeneration, and aberrant chromosome segregation. The gene identified by robl encodes a 97-amino acid polypeptide that is 57% identical (70% similar) to the 105-amino acid Chlamydomonas outer arm dynein-associated protein LC7, also reported here. Both robl and LC7 have homology to several other genes from fruit fly, nematode, and mammals, but not Saccharomyces cerevisiae. Furthermore, we demonstrate that members of this family of proteins are associated with both flagellar outer arm dynein and Drosophila and rat brain cytoplasmic dynein. We propose that roadblock/LC7 family members may modulate specific dynein functions.
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PMID:Drosophila roadblock and Chlamydomonas LC7: a conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis. 1040 68

The functional significance of biochemical and immunochemical heterogeneity in neuronal kinesin remains uncertain. Confocal laser scanning microscopy, cytofluorimetric scanning, and immunoblots were used for quantitative analyses of axonal transport and cellular distribution of immunochemically distinct kinesin heavy chain isoforms (H1 and H2) in rat peripheral nerve and spinal cord. H1 and H2 immunoreactivities (IR) were observed in axons proximal to a crush as early as 1 hr after the crush operation and increased linearly with time, consistent with fast axonal transport of both. Only approximately 10% of the proximal accumulations of H1-IR and H2-IR accumulated distal to the crush, in contrast to synaptophysin-IR (approximately 70%). H2-IR was widely present in peripheral nervous system and virtually colocalized with synaptic vesicle proteins synaptophysin, synaptobrevin I, and SNAP-25 and two neuropeptides [calcitonin gene-related peptide (CGRP) and substance P (SP)], although H2-IR was weaker in spinal cord terminals. In contrast, H1-IR appeared preferentially enriched in large axons, probably motor and large sensory neurons, which contained synaptophysin-IR, synaptobrevin I-IR, SNAP-25-IR, and CGRP-IR. However, H1-IR was weak or absent from SP-containing thin and medium-sized axons. In addition, H1-IR appeared to be absent from spinal cord nerve terminals. H1- and H2-IR kinesins are both transported with fast axonal transport, and comparatively small amounts of kinesins are retrogradely transported. H2 was widely distributed in motor, sensory, and sympathetic neurons, whereas H1 was enriched in large motor and sensory neurons.
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PMID:Axonal transport and distribution of immunologically distinct kinesin heavy chains in rat neurons. 1050 79


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