Disease relevance of alphaTub67C

• Some swallow mutant alleles partially rescue the dominant female sterility of mutations in the atypical 67C alpha-tubulin gene, supporting other studies that suggest a link between RNA localization and the microtubule cytoskeleton [1].

Psychiatry related information on alphaTub67C

• The polarity of kinesin's motor activity can be reversed by MT disassembly and interactions between a motor and a MT end can either slow or speed the rate of tubulin depolymerization [2].

High impact information on alphaTub67C

• Regulation of tubulin gene expression during embryogenesis in Drosophila melanogaster [3].
• Both the polymerization and depolymerization of tubulin have been shown to do work in vitro, but the biochemical complexity of objects moved, such as chromosomes, has complicated the identification of proteins that couple MT dynamics with motility [2].
• Drosophila melanogaster oocytes heterozygous for mutations in the alpha-tubulin 67C gene (alphatub67C) display defects in centromere positioning during prometaphase of meiosis I [4].
• These results suggest that the poleward forces acting at the kinetochore are compromised in the alphatub67C mutants [4].
• We demonstrate that one target of this positive/negative regulation in vivo is the alpha4 integrin, which play a key role in normal hematopoiesis and function of mature leukocytes [5].

Biological context of alphaTub67C

• A large increase in this ratio, achieved by increasing the gene dosage of alpha Tub67C, has little or no effect on meiosis, but severely disrupts mitotic spindle function [6].
• Both meiosis and cleavage-stage mitoses are severely affected by mutations that result in a substantial decrease in the ratio of alpha TUB67C/alpha TUB84B+alpha TUB84D [6].
• The genetic analysis of the alpha Tub67C gene described here demonstrates that alpha TUB67C is required for nuclear division in the oocyte and early embryo [6].
• alpha4-Tubulin is involved in rapid formation of long microtubules to push apart the daughter centrosomes during earlyx Drosophila embryogenesis [7].
• A tassel of short microtubules with two barely separated centrosomes forms in every egg of the Kavar(18c)/+ females, in which the cytoplasm contains both wild-type and Kavar(18c)-encoded alpha4-tubulin with an E82K amino acid substitution (E82K-alpha4-tubulin) [7].

Anatomical context of alphaTub67C

• Enhancement of the ncdD microtubule motor mutant by mutants of alpha Tub67C [8].
• Tubulin dimer (tT) was purified from turkey erythrocytes [9].
• As the LG4-LG5 domain of the alpha4 chain is cleaved in vivo from the main body of laminin-8 (alpha4beta1gamma1), we suggest that the heparan sulphate proteoglycan-binding activity of LG4 is significant in modulating the signalling of Wnt, Decapentaplegic and fibroblast growth factors [10].

Associations of alphaTub67C with chemical compounds

• Imidacloprid bound with very low affinity to the rat alpha4/beta2 nAChR but did so with high affinity to hybrid nAChRs containing Drosophila alpha subunits co-assembled with rat beta2 [11].
• However, replacement of Glu219 by proline in the YXCC motif in loop C of the chimeric alpha4 subunit resulted in a marked displacement to the left of the concentration-response curve for imidacloprid not seen when an equivalent mutation was made in the alpha4beta2 nAChR [12].
• The composite data suggest that the woc gene may regulate 20E-dependent alpha-tubulin detyrosination and that microtubules may be involved in sterol transport and sterol utilization in insect [13].

Physical interactions of alphaTub67C

• 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) [14].

Other interactions of alphaTub67C

• In contrast to these constitutive genes, the tissue-specific alpha 2 and alpha 4 genes code for tubulins with different structures [15].
• Thus, both classes of alpha-tubulin isotype present in the mature oocyte, alpha TUB67C and alpha TUB84B/84D, are essential for normal spindle function in early Drosophila development [6].
• 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 [8].
• These results imply that a specific alpha-tubulin isoform is required for normal cellular function of a kinesin motor protein [8].
• The sequence characteristics of misato indicate either that it arose from an ancestral tubulin-like gene, different parts of which underwent convergent evolution to resemble motifs in the conventional tubulins, or that it arose by the capture of motifs from different tubulin genes [16].

References