A role for the deep orange and carnation eye color genes in lysosomal delivery in Drosophila.

Deep orange and carnation are two of the classic eye color genes in Drosophila. Here, we demonstrate that Deep orange is part of a protein complex that localizes to endosomal compartments. A second component of this complex is Carnation, a homolog of Sec1p-like regulators of membrane fusion.

Genetic dissection of endocytic trafficking in Drosophila using a horseradish peroxidase-bride of sevenless chimera: hook is required for normal maturation of multivesicular endosomes.

Mutations in the hook gene alter intracellular trafficking of internalized ligands in Drosophila. To dissect this defect in more detail, we developed a new approach to visualize the pathway taken by the Bride of Sevenless (Boss) ligand after its internalization into R7 cells. A chimeric protein consisting of HRP fused to Boss (HRP-Boss) was expressed in R8 cells.

Oligomerization of the extracellular domain of Boss enhances its binding to the Sevenless receptor and its antagonistic effect on R7 induction.

In the developing compound eye of Drosophila, neuronal differentiation of the R7 photoreceptor cell is induced by the interaction of the receptor tyrosine kinase Sevenless with its ligand Bride of sevenless (Boss), which is expressed on the neighboring R8 cell. Boss is an unusual ligand of a receptor tyrosine kinase: it is composed of a large extracellular domain, a transmembrane domain with seven membrane-spanning segments and a cytoplasmic tail. Expression of a monomeric, secreted form of the extracellular domain of Boss is not sufficient for Sevenless activation, and instead acts as a weak antagonist.

Cyclosporin A retards the wallerian degeneration of peripheral mammalian axons.

The distal (anucleate) segments of mammalian peripheral axons typically undergo complete Wallerian degeneration within 1-3 days after severance from their cell bodies, unlike invertebrates and lower vertebrates, where anucleate axons do not degenerate for weeks to months. This rapid Wallerian degeneration in mammals could be due to a more efficient immune system and/or to differences in calcium-dependent pathways relative to invertebrates and lower vertebrates. To suppress the immune system and to inhibit calcium-dependent pathways in axons, we gave daily subcutaneous injections of cyclosporin A (CsA: 10 mg/kg) to Sprague-Dawley rats for 7 days before, and 5 days after, severing their right ventral tail nerves.