Control of Golgi Architecture Through Three Centrosome Cohesion Pathways

Abstract

Centrosome cohesion mechanisms link the two interphase centrosomes into a single microtubule-organizing center that is closely associated with the Golgi apparatus. The contribution of cohesion mechanisms to Golgi organization and function remains unclear. Here, we show that rootletin-CEP68 filaments, the C-Nap1-ninein linker, and microtubules derived from subdistal appendages, all of which promote centrosome cohesion, regulate the Golgi through distinct mechanisms while acting synergistically to maintain its organization and function. Centrosome-anchored rootletin-CEP68 filaments associate with AKAP450 through periodic binding of its PACT domain to CEP68 and extend into the Golgi, thereby establishing a physical connection between both organelles. The rootletin-CEP68-AKAP450 linkage even functions in cell types in which rootletin and AKAP450 do not mediate centrosome cohesion, suggesting that Golgi organization is the basic function of these filaments. Knockout analyses demonstrate that the three centrosome cohesion mechanisms collectively regulate Golgi morphology, positioning, and reassembly as well as cell migration. Each mechanism contributes distinctly to the overall process, indicating that they operate as a multifaceted system.