Cell-matrix adhesion controls Golgi organization and function through Arf1 activation in anchorage-dependent cells

Abstract

Cell-matrix adhesion regulates membrane trafficking controlling anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its regulation by adhesion remains unclear. This study finds loss of adhesion to dramatically disorganize the Golgi in mouse and human fibroblast cells. Golgi integrity is restored rapidly on integrin-mediated re-adhesion to fibronectin and disrupted by integrin blocking antibody. In suspended cells, the cis, cis-medial and trans-Golgi differentially disorganize along the microtubule network but show no overlap with the ER making this disorganization distinct from known Golgi fragmentation. This pathway is regulated by adhesion-dependent drop and recovery of Arf1 activation. Constitutively active Arf1 accordingly disrupts this regulation and prevents Golgi disorganization on loss of adhesion. Adhesion-dependent Arf1 activation regulates its binding to the microtubule minus-end motor protein dynein to control Golgi reorganization, which ciliobrevin blocks. Adhesion-dependent Golgi organization controls its function, regulating cell surface glycosylation on loss of adhesion that constitutively active Arf1 blocks. This study hence identifies integrin-dependent cell-matrix adhesion to be a novel regulator of Arf1 activation, controlling Golgi organization and function in anchorage-dependent cells.