Genetic Analyses of Elys Mutations in Drosophila Show Maternal-Effect Lethality and Interactions with Nucleoporin Genes.

ELYS determines the subcellular localizations of Nucleoporins (Nups) during interphase and mitosis. We made loss-of-function mutations of Elys in Drosophila melanogaster and found that ELYS is dispensable for zygotic viability and male fertility but the maternal supply is necessary for embryonic development. Subsequent to fertilization, mitotic progression of the embryos produced by the mutant females is severely disrupted at the first cleavage division, accompanied by irregular behavior of mitotic centrosomes. The Nup160 introgression from D. simulans shows close resemblance to that of the Elys mutations, suggesting a common role for those proteins in the first cleavage division. Our genetic experiments indicated critical interactions between ELYS and three Nup107-160 subcomplex components; hemizygotes of either Nup37, Nup96 or Nup160 were lethal in the genetic background of the Elys mutation. Not only Nup96 and Nup160 but also Nup37 of D. simulans behave as recessive hybrid incompatibility genes with D. melanogaster An evolutionary analysis indicated positive natural selection in the ELYS-like domain of ELYS. Here we propose that genetic incompatibility between Elys and Nups may lead to reproductive isolation between D. melanogaster and D. simulans, although direct evidence is necessary.

Regulation of Drosophila Development by the Golgi Kinase Four-Jointed.

Despite intensive research on kinases and protein phosphorylation, most studies focus on kinases localized to the cytosol and nucleus. Studies in Drosophila discovered a novel signaling pathway that regulates growth and planar cell polarity. In this pathway, the atypical cadherin Fat acts as a receptor, and the cadherin Dachsous (Ds) serves as its ligand. Genetic studies in Drosophila identified the four-jointed gene as a regulator of the Fat pathway. Four-jointed (Fj) resides in the Golgi and phosphorylates the cadherin domains of Fat and Ds. Fj-mediated phosphorylations promote the ability of Fat to bind to its ligand Ds and inhibit the ability of Ds to bind Fat, which is biased toward a stronger effect on Fat. Fj is expressed in a gradient in many developing tissues. The Fat-Ds-binding gradient can be explained by the graded activity of Fj that is sufficient to propagate the polarization of complexes across whole tissues. Recent studies revealed a new class of kinases that localize within the secretory pathway and the extracellular space, and phosphorylate proteins and sugar chains in the secretory pathway. Further, they appear to regulate extracellular processes. Mutations of the genes encoding these kinases cause human disease, thus underscoring the biological importance of phosphorylation events within the secretory pathway.