TheDrosophilaEGFR ligand mSpitz is delivered to cytoplasmic capes at sites of non-canonical RNA export on the nuclear envelopeviathe endosomal system

Nuclear-cytoplasmic communication is not limited to nuclear pores, with both proteins and RNA using alternative routes between these compartments. We previously characterized cytoplasmic capes (large invaginations of the nuclear envelope in Drosophila ), which are enriched for the membrane-bound EGF receptor ligand mSpitz, endosome-related organelles and ubiquitylated proteins. Closely associated with capes are groups of perinuclear vesicles resembling those seen at sites of RNP export via a budding mechanism. Here, we demonstrate that mSpitz delivery to capes requires passage through the endosomal system. We also show that capes are closely associated with sites of non-canonical RNP export as well as the dFrizzled2 receptor C terminal fragment, a core component of this export pathway. Video microscopy of glands in intact larvae indicates that cytoplasmic capes are stable structures that persist for at least 90 minutes without conspicuous growth. We further show that capes appear with the growth of the salivary gland rather than its developmental stage. Finally, we show that the large F-actin binding protein β H -spectrin, which modulates endosomal trafficking, as well as its partner α-spectrin are required for cape formation. Cytoplasmic capes therefore represent a subspecialization of the nuclear envelope where endosomal trafficking and RNP export are closely associated. Synopsis We further characterize large invaginations of the nuclear envelope called cytoplasmic capes in Drosophila . The EGF receptor ligand mSpitz is concentrated in capes and we show that it traffics to this compartment via endosomes. The presence of RNP and the dFrizzled2 receptor C-terminal fragment also indicates that non-canonical RNA export is concentrated at capes. In vivo imaging shows that capes persist for at least 90 minutes. Finally, the large F-actin crosslinker α/β ◻ -spectrin is shown to be required for cape formation. Abstract Figure