Efficient Golgi Forward Trafficking Requires GOLPH3-Driven, PI4P-Dependent Membrane Curvature

Summary Vesicle budding for Golgi-to-plasma membrane trafficking is a key step in secretion. Proteins that induce curvature of the Golgi membrane are predicted to be required, by analogy to vesicle budding from other membranes. Here, we demonstrate that GOLPH3, upon binding to the phosphoinositide PI4P, induces curvature of synthetic membranes in vitro and the Golgi in cells. Moreover, efficient Golgi-to-plasma membrane trafficking critically depends on the ability of GOLPH3 to curve the Golgi membrane. Interestingly, uncoupling of GOLPH3 from its binding partner MYO18A results in extensive curvature of Golgi membranes, producing dramatic tubulation of the Golgi, but does not support forward trafficking. Thus, forward trafficking from the Golgi to the plasma membrane requires the ability of GOLPH3 both to induce Golgi membrane curvature and to recruit MYO18A. These data provide fundamental insight into the mechanism of Golgi trafficking and into the function of the unique Golgi secretory oncoproteins GOLPH3 and MYO18A.