Disease relevance of ncd

• Here we describe the expression of ncd protein in E. coli and the initial characterization of the ncd protein's motor properties [1].

Psychiatry related information on ncd

• The characteristics of the NcdD motor explain its meiotic loss of function, and are consistent with partial motor activity of Ncd being sufficient for its mitotic, but not its meiotic, role [2].

High impact information on ncd

• Members of the kinesin superfamily share a similar motor catalytic domain yet move either toward the plus end (e.g., conventional kinesin) or the minus end (e.g., Ncd) of microtubules [3].
• Here, we show that kinesin's catalytic domain (316 residues) in a dimeric construct (560 residues) can be replaced with the catalytic domain of Ncd and that the resultant motor moves in the kinesin direction [3].
• Finally, the clone we isolated appears to correspond to the non-claret disjunctional (ncd) gene, which when mutant causes defects in meiotic and early embryonic mitotic chromosome segregation, and whose recently determined sequence predicts a kinesin-like domain [4].
• The Drosophila ncd gene is required for chromosome segregation during female meiosis [1].
• A single kinesin head bound to a microtubule has a pear-shaped structure, with the broader end towards the 'plus' end of the microtubule under all conditions; the reverse motor, ncd, is similarly oriented [5].

Biological context of ncd

• Nuclear defects were incompletely suppressed; micronuclei formed near telophase at the poles of bipolar spindle in klp61F ncd spermatocytes [6].
• In female meiosis, sub mutations have a similar phenotype to ncd; even though chromosomes are joined by chiasmata they fail to segregate at meiosis I [7].
• Analysis of mutant oocytes indicates that the Non-Claret Disjunctional (NCD) kinesin-like protein is required for normal spindle assembly kinetics and stabilization of the spindle during metaphase arrest [8].
• Anastral meiotic spindle morphogenesis: role of the non-claret disjunctional kinesin-like protein [8].
• Our results are consistent with a model in which KLP61F prevents Ncd-mediated collapse of a nonmicrotubule matrix derived from the interphase nucleus [6].

Anatomical context of ncd

• Based on these observations, we propose that microtubule bundling by the NCD kinesin-like protein promotes assembly of a stable bipolar spindle in the absence of typical MTOCs [8].
• The precociously split and free centrosomes indicate that the Ncd motor acts in cleavage stage embryos to maintain centrosome integrity and attachment to nuclei [9].
• Using antibodies directed against nonconserved regions of the protein, we have localized the ncd motor protein to the meiotic and early mitotic spindle, and to spindles in a mitotically dividing cultured cell line [10].

Associations of ncd with chemical compounds

• Our previous work on the MT-binding site of the Ncd tail domain demonstrated that this site, like the MT-binding sites of tau, contains basic residues flanked by proline residues and can promote MT assembly and stability [11].
• Null mutant females expressing the Ncd motor fused to the Aequorea victoria green fluorescent protein (GFP), regulated by the wild-type ncd promoter, are rescued for chromosome segregation and embryo viability [9].
• A significant difference between ncd and cytoplasmic dynein was their relative sensitivity to vanadate and to aluminum fluoride [12].
• Superposition of the structures of ncd and myosin subfragment 1 reveals that the labeled cysteine is very close to the region which is homologous to the helix containing the two reactive sulfhydryls in myosin and is approximately 10 A from the junction of the motor domain with the remainder of the molecule [13].
• We removed ADP from the ncd motor domain by gel filtration in the presence of EDTA and high salt [14].

Physical interactions of ncd

• To determine the tubulin subunit(s) involved in binding to ncd, mixtures of ncd motor domain and MTs were treated with the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide) (EDC) [15].

Regulatory relationships of ncd

• Novel nuclear defects in KLP61F-deficient mutants in Drosophila are partially suppressed by loss of Ncd function [6].

Other interactions of ncd

• We propose that the polar localization of Msps mediated by D-TACC and Ncd may be crucial for the stabilization of meiotic spindle bipolarity [16].
• The genetics and cytology of doubly mutant embryos and the molecular defect of NcdD provide evidence for interaction of Ncd with alpha Tub67C in vivo [17].
• Ncd is a kinesin-related microtubule motor protein required for chromosome segregation in Drosophila oocytes and early embryos [17].
• Kinetic analysis suggests that KLP3A contributes to spindle pole separation during the prometaphase-to-metaphase transition (when it antagonizes Ncd) and anaphase B, to normal rates of chromatid motility during anaphase A, and to the proper spacing of daughter nuclei during telophase [18].
• A more severe ncd mutant that probably lacks ATPase activity prevents formation of lateral interactions between chromosomes and causes defective microtubule elongation [19].

Analytical, diagnostic and therapeutic context of ncd

• Immunofluorescence microscopy indicated that non-claret disjunctional (Ncd) is a component of the nuclear matrix in somatic cells and spermatocytes [6].
• Here we report the crystal structure of the MgADP complex of the Drosophila ncd motor domain determined to 2.5A by X-ray crystallography, and compare it to the kinesin structure [20].
• We used cryo-electron microscopy and image reconstruction to investigate the structure and microtubule-binding configurations of dimeric non-claret disjunctional (ncd) motor domains under various nucleotide conditions, and applied molecular docking using ncd's dimeric X-ray structure to generate a mechanistic model for force transduction [21].
• Molecular cloning and expression of the Caenorhabditis elegans klp-3, an ortholog of C terminus motor kinesins Kar3 and ncd [22].
• We have calculated a three-dimensional map of tubulin sheets decorated with monomeric recombinant ncd motor domains by negative-stain electron microscopy and image analysis [23].

References