Blagoveshchenskaya et al. The enzyme's removal from the Golgi increases trafficking when cells need it most.
Growing cells need new proteins and lipids delivered to the expanding plasma membrane. The outward transport of these components from the Golgi is driven in part by a pool of PI4P phospholipid, which is thought to help create a suitable lipid environment for the formation of Golgi-derived carriers. The new findings reveal that Golgi PI4P levels rise when cells get a taste of extracellular growth factors.
In dormant cells, PI4P levels at the Golgi were kept low by a phosphatase called SAC1, which turns PI4P to PI. To reach the Golgi, SAC1 formed oligomers that seem to uncover a binding motif that recruits it into ER-to-Golgi transport vesicles.
The oligomers were disrupted when cells were given growth factors to jolt them out of dormancy. Both FGF and PDGF activated the ERK1/2 and p38 MAPK pathways, which led to disassembly of SAC1 oligomers. Collapse of the oligomers caused SAC1 relocation to the ER, thereby allowing Golgi PI4P levels to rise.
Constitutive activation of p38 was enough to nudge cells out of quiescence and back into proliferation, as occurs during early stages of cancer. The group will soon test whether SAC1 is necessary for this rejuvenation.