GORAB, a Golgi protein required for centriole structure and duplication

Abstract

Genome wide screens are widely believed to have identified the great majority of genes required for centriole duplication. However, seeking to clarify the partners of the Drosophila cartwheel protein Sas6, we identified Gorab, a known trans-Golgi associated protein that is mutated in the human wrinkly skin disease, gerodermia osteodysplastica. We now report that Gorab is present not only in the trans-Golgi but also in association with Sas6 at the core of the centriole. Flies lacking Gorab show defects in centriole duplication in many tissues and are also uncoordinated due to basal body defects in sensory cilia, which lose their 9-fold symmetry. We demonstrate the separation of centriole and Golgi functions of Drosophila Gorab in two ways: First, we have created Gorab variants that are unable to localize to trans-Golgi but can still rescue the centriole and cilia defects of gorab null flies. Secondly, we show that expression of Cterminally tagged Gorab disrupts Golgi functions in cytokinesis of male meiosis, a dominant phenotype overcome by a second mutation preventing Golgi targeting. We discuss the tissue specific requirement of Gorab for centriole duplication in the context of its split functions.