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Kun-liang Guan - One of the best experts on this subject based on the ideXlab platform.

  • The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak.
    The Journal of biological chemistry, 2004
    Co-Authors: Kun-liang Guan
    Abstract:

    The Down syndrome cell adhesion molecule (DSCAM) is a member of the immunoglobulin superfamily that maps to a Down syndrome region of chromosome 21q22.2-22.3. In Drosophila, Dscam functions as an axon guidance receptor regulating targeting and branching. Genetic and biochemical studies have shown that in Drosophila, Dscam activates Pak1 via the Dock adaptor molecule. The extracellular domain of human DSCAM is highly homologous to the Drosophila protein; however, the intracellular domains of both human and Drosophila DSCAM share no obvious sequence identity. To study the signaling mechanisms of human DSCAM, we investigated the interaction between DSCAM and potential downstream molecules. We found that DSCAM directly binds to Pak1 and stimulates Pak1 phosphorylation and activity, unlike Drosophila where an adaptor protein Dock mediates the interaction between Dscam and Pak1. We also observed that DSCAM activates both JNK and p38 MAP kinases. Furthermore, expression of the cytoplasmic domain of DSCAM induces a morphological change in cultured cells that is JNK-dependent. These observations suggest that human DSCAM also signals through Pak1 and may function in axon guidance similar to the Drosophila Dscam.

Kurtis Kiesewetter - One of the best experts on this subject based on the ideXlab platform.

  • Human down syndrome cell adhesion molecules (DSCAMs) are functionally conserved with Drosophila Dscam[TM1] isoforms in controlling neurodevelopment
    Insect biochemistry and molecular biology, 2011
    Co-Authors: Jianhua Huang, Ying Wang, Sangeetha Raghavan, Siqian Feng, Kurtis Kiesewetter
    Abstract:

    Drosophila Down syndrome cell adhesion molecule (Dscam) potentially produces more than 150,000 cell adhesion molecules that share two alternative transmembrane/juxtamembrane (TM) domains, which dictate the dendrite versus axon subcellular distribution and function of different Dscam isoforms. Vertebrate genomes contain two closely related genes, DSCAM and DSCAM-Like1 (DSCAML1), which do not have extensive alternative splicing. We investigated the functional conservation between invertebrate Dscams and vertebrate DSCAMs by cross-species rescue assays and found that human DSCAM and DSCAML1 partially, but substantially, rescued the larval lethality of Drosophila Dscam mutants. Interestingly, both human DSCAM and DSCAML1 were targeted to the dendrites in Drosophila neurons, had synergistic rescue effects with Drosophila Dscam[TM2], and preferentially rescued the dendrite defects of Drosophila Dscam mutant neurons. Therefore, human DSCAM and DSCAML1 are functionally conserved with Drosophila Dscam[TM1] isoforms.

Daniel L. Hartl - One of the best experts on this subject based on the ideXlab platform.

  • Codon usage bias and base composition of nuclear genes in Drosophila.
    Genetics, 1993
    Co-Authors: Etsuko N. Moriyama, Daniel L. Hartl
    Abstract:

    The nuclear genes of Drosophila evolve at various rates. This variation seems to correlate with codon-usage bias. In order to elucidate the determining factors of the various evolutionary rates and codon-usage bias in the Drosophila nuclear genome, we compared patterns of codon-usage bias with base compositions of exons and introns. Our results clearly show the existence of selective constraints at the translational level for synonymous (silent) sites and, on the other hand, the neutrality or near neutrality of long stretches of nucleotide sequence within noncoding regions. These features were found for comparisons among nuclear genes in a particular species (Drosophila melanogaster, Drosophila pseudoobscura and Drosophila virilis) as well as in a particular gene (alcohol dehydrogenase) among different species in the genus Drosophila. The patterns of evolution of synonymous sites in Drosophila are more similar to those in the prokaryotes than they are to those in mammals. If a difference in the level of expression of each gene is a main reason for the difference in the degree of selective constraint, the evolution of synonymous sites of Drosophila genes would be sensitive to the level of expression among genes and would change as the level of expression becomes altered in different species. Our analysis verifies these predictions and also identifies additional selective constraints at the translational level in Drosophila.

  • Identification of nucleotide substitutions necessary for trans-activation of mariner transposable elements in Drosophila: analysis of naturally occurring elements.
    Genetics, 1991
    Co-Authors: K Maruyama, K D Schoor, Daniel L. Hartl
    Abstract:

    Six copies of the mariner element from the genomes of Drosophila mauritiana and Drosphila simulans were chosen at random for DNA sequencing and functional analysis and compared with the highly active element Mos1 and the inactive element peach. All elements were 1286 base pairs in length, but among them there were 18 nucleotide differences. As assayed in Drosophila melanogaster, three of the elements were apparently nonfunctional, two were marginally functional, and one had moderate activity that could be greatly increased depending on the position of the element in the genome. Both molecular (site-directed mutagenesis) and evolutionary (cladistic analysis) techniques were used to analyze the functional effects of nucleotide substitutions. The nucleotide sequence of the element is the primary determinant of function, though the activity level of elements is profoundly influenced by position effects. Cladistic analysis of the sequences has identified a T -> A transversion at position 1203 (resulting in a Phe -> Leu amino acid replacement in the putative transposase) as being primarily responsible for the low activity of the barely functional elements. Use of the sequences from the more distantly related species, Drosophila yakuba and Drosophila teissieri, as outside reference species, indicates that functional mariner elements are ancestral and argues against their origination by a novel mutation or by recombination among nonfunctional elements.

Charlotte Helfrich-förster - One of the best experts on this subject based on the ideXlab platform.

  • Rhodopsin 7–The unusual Rhodopsin in Drosophila
    PeerJ, 2016
    Co-Authors: Pingkalai R. Senthilan, Charlotte Helfrich-förster
    Abstract:

    : Rhodopsins are the major photopigments in the fruit fly Drosophila melanogaster. Drosophila express six well-characterized Rhodopsins (Rh1-Rh6) with distinct absorption maxima and expression pattern. In 2000, when the Drosophila genome was published, a novel Rhodopsin gene was discovered: Rhodopsin 7 (Rh7). Rh7 is highly conserved among the Drosophila genus and is also found in other arthropods. Phylogenetic trees based on protein sequences suggest that the seven Drosophila Rhodopsins cluster in three different groups. While Rh1, Rh2 and Rh6 form a "vertebrate-melanopsin-type"-cluster, and Rh3, Rh4 and Rh5 form an "insect-type"-Rhodopsin cluster, Rh7 seem to form its own cluster. Although Rh7 has nearly all important features of a functional Rhodopsin, it differs from other Rhodopsins in its genomic and structural properties, suggesting it might have an overall different role than other known Rhodopsins.

Jianhua Huang - One of the best experts on this subject based on the ideXlab platform.

  • Human down syndrome cell adhesion molecules (DSCAMs) are functionally conserved with Drosophila Dscam[TM1] isoforms in controlling neurodevelopment
    Insect biochemistry and molecular biology, 2011
    Co-Authors: Jianhua Huang, Ying Wang, Sangeetha Raghavan, Siqian Feng, Kurtis Kiesewetter
    Abstract:

    Drosophila Down syndrome cell adhesion molecule (Dscam) potentially produces more than 150,000 cell adhesion molecules that share two alternative transmembrane/juxtamembrane (TM) domains, which dictate the dendrite versus axon subcellular distribution and function of different Dscam isoforms. Vertebrate genomes contain two closely related genes, DSCAM and DSCAM-Like1 (DSCAML1), which do not have extensive alternative splicing. We investigated the functional conservation between invertebrate Dscams and vertebrate DSCAMs by cross-species rescue assays and found that human DSCAM and DSCAML1 partially, but substantially, rescued the larval lethality of Drosophila Dscam mutants. Interestingly, both human DSCAM and DSCAML1 were targeted to the dendrites in Drosophila neurons, had synergistic rescue effects with Drosophila Dscam[TM2], and preferentially rescued the dendrite defects of Drosophila Dscam mutant neurons. Therefore, human DSCAM and DSCAML1 are functionally conserved with Drosophila Dscam[TM1] isoforms.