FIGURE 4.

Putative mechanism of BARS-mediated membrane fission during post-Golgi carrier formation. Schematic representation of tubular carrier precursor that emerged out of specialized TGN-export domain during the budding/tubulation step (I), a process that precedes membrane fission (II). Upon fission event, the free post-Golgi carriers are released and directed toward the basolateral plasma membrane (usually with the employment of microtubular tracks and microtubule-based motors). At the protein level: upon activation ARF recruits PI4KIIIβ and PKD kinases onto the Golgi membranes and activates the PI4KIIIβ kinase leading to PtdInsP4 production. PI4KIIIβ kinase can be also activated by NCS-1, a well-known ARF interactor. ARF and the produced PtdInsP4-membrane pool promote the recruitment of FAPPs, which endorse membrane bending and budding/tubulation. PI4KIIIβ and BARS are then phosphorylated by PKD and PAK1, respectively (see text for details) allowing to the formation of a tripartite core complex where the phosphorylated kinase-active form of PI4KIIIβ is bridged to the phosphorylated fission-active form of BARS through 14-3-3γ dimer. Once incorporated into this complex, BARS binds to and activates LPAATδ enzyme leading to the local membrane conversion of LPA into PA. At the lipid level this enzymatic conversion of LPA into PA is central for the completion of the fission event. This figure is created using the web-based tool BioRender (https://biorender.com/library/).