YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3ζ

TLDR

The Golgi apparatus directs secretion to specific plasma membrane sites in response to extracellular signals, yet how signaling events coordinate with Golgi function remains poorly understood. This study seeks to uncover a scaffolding role for the Golgi matrix protein GM130 that explains how such signaling events are regulated. The authors show that GM130 serves as a scaffold that recruits and activates signaling components at the Golgi. YSK1 and MST4 are recruited to the Golgi by GM130, where GM130 binding triggers their autophosphorylation; loss of YSK1 disrupts perinuclear Golgi organization, cell migration, and collagen invasion, and YSK1 phosphorylates 14‑3‑3ζ, linking Golgi signaling to transport, adhesion, and polarity pathways.

Abstract

The Golgi apparatus has long been suggested to be important for directing secretion to specific sites on the plasma membrane in response to extracellular signaling events. However, the mechanisms by which signaling events are coordinated with Golgi apparatus function remain poorly understood. Here, we identify a scaffolding function for the Golgi matrix protein GM130 that sheds light on how such signaling events may be regulated. We show that the mammalian Ste20 kinases YSK1 and MST4 target to the Golgi apparatus via the Golgi matrix protein GM130. In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. A biochemical screen identifies 14-3-3ζ as a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport events, cell adhesion, and polarity complexes important for cell migration.