# Akt-elicited phosphorylation of Acapin steers cell migration

## TL;DR

This study reveals how Akt signaling promotes cell migration by regulating Acapin, which controls ARF6 activity in lamellipodia.

## Contribution

The paper identifies Acapin as a novel Akt-regulated protein that modulates ARF6 activity to drive cell migration.

## Key findings

- Acapin inhibits ACAP4's GAP activity to activate ARF6 in vitro.
- Akt signaling recruits Acapin to lamellipodia via phosphorylation at Ser247.
- Acapin is essential for EGF–Akt signaling to stimulate efficient cell migration.

## Abstract

Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia. However, the molecular mechanisms underlying dynamic recruitment of vesicular membrane during cell migration remain elusive. Here, we report a critical mechanism underlying epidermal growth factor (EGF)-elicited Akt signaling-steered cell migration. Using functional proteomics screen, we identified a novel ADP-ribosylation factor 6 (ARF6)–ACAP4 signaling regulator, Acapin, which inhibits the GTPase-activating protein (GAP) activity of ACAP4 to activate ARF6 GTPase in vitro. In cells, EGF stimulation elicits Akt signaling, which recruits Acapin to the lamellipodium membrane via phosphorylation of Acapin at its Ser247 residue and enhances the binding of Acapin to ACAP4 to elevate the ARF6-GTP level. Therefore, Acapin is required for efficiently stimulating cell migration by EGF–Akt signaling. Together, our results demonstrate the role of Acapin in relaying the Akt signaling cascade during cell migration processes.