Poster Presentation 2014 International Biophysics Congress

The GSK3 beta-Dzip1-Rab8 cascade regulates ciliogenesis after mitosis (#618)

Boyan Zhang , Tingting Zhang , Guopeng Wang , Qing Jiang , Chuanmao Zhang

The primary cilium is an antenna-like organelle that projects from the apical surface of most vertebrate cells and plays pivotal roles in mediating signal transduction and regulating the balance between proliferation and differentiation. It consists of a basal body, a microtubule-based axoneme generated from the basal body, and sheathed by a signaling receptor-rich ciliary membrane extending from the cell membrane. The structure of primary cilium is dynamic during the cell cycle with assembly after mitosis and resorption before the mitotic entry. However, how ciliogenesis is regulated remains largely unknown. In this work, we show Dzip1 plays a crucial role during the ciliogenesis. Dzip1 is a zinc-finger protein that is predominantly expressed in human embryonic stem cells, fetal, and adult germ cells. It is first identified in zebrafish as iguana, mutation of which results in cilia shortening or absence in the Kupffer's vesicles. In cultured mammalian cells, it has been shown that Dzip1 and a Dzip1-like protein, Dzip1L, are required for primary cilia formation. Here we demonstrate that Dzip1 is concentrated inside the periciliary diffusion barrier and at the mother centriole in resting cells. In cycling cells, it is localized to the centrosome of the grandmother centriole-containing daughter cell earlier than the other daughter cell after mitosis. At the centrosome/basal body, Dzip1 regulates ciliogenesis through regulating Rab8 GTPase cycle and entry of Rab8 into the cilium. We also found that Dzip1 is phosphorylated by GSK3 beta, which is increasingly activated during the mitosis to interphase transition. Collectively, our data reveal a unique GSK3 beta-Dzip1-Rab8 pathway in the ciliogenesis regulation after mitosis.