Disease relevance of byn

• Previous studies have shown that the Drosophila cation channels designated Trp and Trpl can be functionally expressed in Sf9 insect cells using baculovirus expression vectors [1].

High impact information on byn

• In the absence of the Hh pathway, cad induces internal analia development, probably by activating the brachyenteron and even-skipped genes [2].
• Reporter assays and site-directed mutagenesis demonstrate that Brachyenteron binding sites confer in part additive, in part synergistic effects on otp transcription levels [3].
• Drosophila embryos deficient for Trg do not form the hindgut, a phenotype that can be rescued by a Trg transgene [4].
• This conservation and the high similarity of T and Trg raise the question of a common evolutionary origin of the hindgut of insects and the notochord of chordates [4].
• The fru gene encodes a putative transcription factor with a BTB domain and two zinc-finger motifs, and with consensus Tra-binding sequences [5].

Biological context of byn

• In byn mutant embryos, the defective program of gene activity in these primordia is followed by apoptosis (initiated by reaper expression and completed by macrophage engulfment), resulting in severely reduced hindgut and anal pads [6].
• Drosophila brachyenteron regulates gene activity and morphogenesis in the gut [6].
• These mutations constitute an allelic series and are all rescued to viability by a Trg transgene [6].
• The binding of Tra to these sequences results in sex-specific alternative splicing of the fru mRNA, leading to production of the 'male-type' or 'female-type' Fru protein [5].
• We find that this repressor form of Tailless behaves like the intact protein in gain- and loss-of-function experiments, being sufficient to support normal embryonic development and establish accurate patterns of gene expression even for positive Tailless targets such as hunchback and brachyenteron [7].

Anatomical context of byn

• Although byn is not expressed in the midgut or the Malpighian tubules, it is required for the formation of midgut constrictions and for the elongation of the Malpighian tubules [6].
• Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+) store depletion [8].
• This is the first function described for brachyenteron or fork head in the mesoderm of Drosophila [9].
• The Drosophila proteins, Trp and Trpl, are suggested to be cation channels responsible for depolarization of the receptor potential associated with stimulation of insect photoreceptor cells by light [10].
• In embryos mutant for the various alleles, relative levels of blastoderm expression of Trg (T-related gene, required to establish the hindgut) and of mature hindgut size were determined; the results of these assays correlated with each other [11].

Associations of byn with chemical compounds

• Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting domains, one on Trp and two on IP(3)R [8].
• Expression of these genes in various mammalian cells has provided evidence that Trp proteins form plasma membrane Ca2+-permeant channels that can be activated by an agonist that activates phospholipase C, by inositol 1,4, 5-trisphosphate, and/or store depletion [12].
• Many of the HN-HN NOEs are consistent with models containing compact residual nativelike secondary structure and greater exposure of the Trp 36 indole to solvent, similar to kinetic intermediates formed in the hierarchic condensation model of folding [13].
• Forty to 46% of the eukaryotic tryptic peptides contain Cys, Met, or Trp [14].
• However, the methyl and aromatic NOE data better fit conformations with non-native burial of the Trp indole surrounded by hydrophobic groups and more loosely formed beta-structure; these structural characteristics are more consistent with those of kinetic intermediates formed during the hydrophobic collapse mechanism of folding [13].

Other interactions of byn

• Genes that are required for patterning of embryonic epithelia (e.g., tailless, Krüppel, fork head, and brachyenteron) or for progression of the morphogenetic furrow (i. e., hedgehog) are required to establish or maintain the regional expression of arc [15].
• Supported by fork head, brachyenteron mediates the early specification of the CVM along with zinc-finger homeodomain protein-1 [9].
• Functions for Drosophila brachyenteron and forkhead in mesoderm specification and cell signalling [9].
• The handedness of particular gut parts was randomized or became symmetric in mutants of brachyenteron, huckebein and patched, suggesting that different gene pathways can interfere in determining LR asymmetry of the gut [16].

Analytical, diagnostic and therapeutic context of byn

• Based on structure and sequence analysis of several homeodomains, we deduce that quenching is due to a transient, excited-state NH ellipsis pi hydrogen bond involving Trp 48 and a conserved aromatic residue at position 8 [17].

References