Disassembly of Axonal G3BP1 Aggregates by a Casein Kinase 2α mRNA Translational Switch

Abstract

The main limitation on axon regeneration in the peripheral nervous system (PNS) is the slow rate of regrowth.  We recently demonstrated that nerve regeneration can be accelerated by axonal G3BP1 aggregate disassembly, releasing axonal mRNAs for local translation to support growth.  Here we show that G3BP1 phosphorylation by Casein Kinase 2α (CK2α) regulatesdisassembly of mRNA storage structures in injured sensory neurons.  Axonal CK2α activity is temporally and spatially restricted by mTOR and calcium dependent local translation of Csnk2a1 mRNA in axons after injury.  CK2α appearance in axons after PNS nerve injury correlates with disassembly of axonal stress granule-like aggregates and increased axon growth.  Changes in axoplasmic calcium enableaxonal translation to switch from early synthesis of proteins needed for retrograde injury signaling to later synthesis of growth-promoting proteins from mRNA pools released by CK2α regulation of G3BP1.  Hence, calcium-dependent G3BP1 phosphorylation regulates neuronal regeneration.

Keywords: CK2α, stress granule, axonal protein synthesis, axon growth