Disease relevance of betaTub60D

• This model system implicates the cellular T antigen-binding proteins, such as Rb and p53, in the pathogenesis of bone and soft tissue neoplasms in mice [1].

Psychiatry related information on betaTub60D

• 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 betaTub60D

• Molecular biology and genetics of tubulin [3].
• Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles [4].
• The expression of beta 3-tubulin is accompanied by a coordinate transient increase in the level of synthesis of the embryonic alpha-tubulins, thereby maintaining an approximately equimolar synthesis of alpha- and beta-tubulin subunits throughout embryogenesis [5].
• Synthesis of beta 3-tubulin in vitro in a rabbit reticulocyte translation system is directed by RNA extracted from embryos only at the stage when the protein is expressed [5].
• In situ hybridization experiments show that both the alpha- and beta-tubulin multigene families have dispersed arrangements on the chromosome [6].

Biological context of betaTub60D

• Examination of beta3 mutant phenotypes showed that beta3 is required for axonal patterning and connectivity and for spatial positioning within the optic lobe [7].
• Drosophila beta3-tubulin is an essential isoform expressed during differentiation of many cell types in embryos and pupae [7].
• We also demonstrate that the first intron of the beta 3-tubulin gene bears a tissue-specific enhancer element that is required for expression in the visceral muscles and that also functions efficiently when cloned downstream of an indicator gene [8].
• The genomic DNA sequence and deduced amino acid sequence are presented for three Drosophila melanogaster beta-tubulins: a developmentally regulated isoform beta 3-tubulin, the wild-type testis-specific isoform beta 2-tubulin, and an ethyl methanesulfonate-induced assembly-defective mutation of the testis isoform, B2t8 [9].
• So this element is likely to be a target of homeotic genes, which would define the beta 3 tubulin gene as a realisator gene under the control of selector genes [10].

Anatomical context of betaTub60D

• Our data support the hypothesis that beta3 confers specialized properties on the microtubules into which it is incorporated [7].
• The separability of elements driving beta 3-tubulin expression in the somatic and visceral mesoderm facilitates the investigation of the different programs involved in regulating the early differentiation of this germ layer [8].
• We show that expression of the beta 3-tubulin gene in the somatic muscles, the pharyngeal muscles, and the dorsal vessel is mediated by far upstream sequences [8].
• A lethal complementation group comprising mutations in the beta 3-tubulin gene (beta Tub60D) was identified by rescue of their lethality by a wild-type copy of the gene introduced into the genome via P element-mediated germ line transformation [11].
• Thus transient zygotic beta3 expression has permanent consequences for the architecture of the cap cell microtubule cytoskeleton in the larval sensilla, even when beta3 is no longer present [12].

Associations of betaTub60D with chemical compounds

• Intron and upstream sequences regulate expression of the Drosophila beta 3-tubulin gene in the visceral and somatic musculature, respectively [8].
• Expression of a new beta tubulin subunit is induced by 20-hydroxyecdysone in Drosophila cultured cells [13].
• The expression of the beta 3 tubulin gene is regulated, at the transcriptional level, by the steroid hormone ecdysone, in Drosophila Kc cells [14].
• We have used negative-stain electron microscopy and image analysis to study the structures of microtubules and tubulin sheets decorated with the motor domain (head) of kinesin in three states: in the presence of an unhydrolysable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP); without nucleotides; and with adenosine 5'-diphosphate (ADP) [15].
• Each tubulin monomer binds a guanine nucleotide, which is nonexchangeable when it is bound in the alpha subunit, or N site, and exchangeable when bound in the beta subunit, or E site [16].

Physical interactions of betaTub60D

• E3KARP up-regulates the PLC-beta3 activation coupled to muscarinic receptor [17].
• Nucleotide-dependent angular change in kinesin motor domain bound to tubulin [15].
• Finally, two different sets of Engrailed binding sites are shown to be involved in the early and late regulation of beta3-tubulin by Engrailed during embryogenesis [18].
• Thus, these two Tinman binding sites act in concert to drive beta3 tubulin gene expression during heart development [19].

Regulatory relationships of betaTub60D

• Axonemal defects caused by alpha 85E are precisely reciprocal to dominant defects in doublet microtubules we observed in a previous study of ectopic germ-line expression of the developmentally regulated beta 3-tubulin isoform [20].
• beta3-tubulin is directly repressed by the engrailed protein in Drosophila [18].
• Tinman regulates the transcription of the beta3 tubulin gene (betaTub60D) in the dorsal vessel of Drosophila [19].

Other interactions of betaTub60D

• Comparison of the phenotypes of beta3 mutations with those that result from disruption of the Hedgehog signaling pathway shows that beta3 functions early in the establishment of the adult visual system [7].
• In addition, PLC-beta3 specifically interacts with E3KARP, another protein closely related to NHERF, through its C-terminal PDZ-binding motif [17].
• Double staining for beta 1 tubulin gene expression in apodemes and for beta 3 tubulin gene expression in muscles allowed us to correlate apodeme and muscle formation [21].
• The mutation B2t8 in the gene for the testis-specific beta 2-tubulin defines a single amino acid residue required for normal assembly function of beta-tubulin [9].
• Ultrabithorax is a regulator of beta 3 tubulin expression in the Drosophila visceral mesoderm [10].

Analytical, diagnostic and therapeutic context of betaTub60D

• Structure of the alpha beta tubulin dimer by electron crystallography [16].
• 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 [22].
• By two-dimensional gel electrophoresis of tubulins prepared from tissues of Drosophila melanogaster we have identified a beta-tubulin subunit that is present only in the testis [23].
• This protein at substoichometric concentration promotes the polymerization of tubulin into double-walled tubules and polymorphic aggregates or bundles paclitaxel-stabilized microtubules as judged by quantitative data of electron and atomic force microscopies [24].
• Both wild-type and mutant testis-specific beta-tubulins were characterized by vinblastine sulfate precipitation, coassembly with purified Drosophila embryo tubulin, and peptide mapping [23].

References