| First Author | Sahoo PK | Year | 2020 |
| Journal | Curr Biol | Volume | 30 |
| Issue | 24 | Pages | 4882-4895.e6 |
| PubMed ID | 33065005 | Mgi Jnum | J:330663 |
| Mgi Id | MGI:6821638 | Doi | 10.1016/j.cub.2020.09.043 |
| Citation | Sahoo PK, et al. (2020) A Ca(2+)-Dependent Switch Activates Axonal Casein Kinase 2alpha Translation and Drives G3BP1 Granule Disassembly for Axon Regeneration. Curr Biol 30(24):4882-4895.e6 |
| abstractText | The main limitation on axon regeneration in the peripheral nervous system (PNS) is the slow rate of regrowth. We recently reported that nerve regeneration can be accelerated by axonal G3BP1 granule disassembly, releasing axonal mRNAs for local translation to support axon growth. Here, we show that G3BP1 phosphorylation by casein kinase 2alpha (CK2alpha) triggers G3BP1 granule disassembly in injured axons. CK2alpha activity is temporally and spatially regulated by local translation of Csnk2a1 mRNA in axons after injury, but this requires local translation of mTor mRNA and buffering of the elevated axonal Ca(2+) that occurs after axotomy. CK2alpha's appearance in axons after PNS nerve injury correlates with disassembly of axonal G3BP1 granules as well as increased phospho-G3BP1 and axon growth, although depletion of Csnk2a1 mRNA from PNS axons decreases regeneration and increases G3BP1 granules. Phosphomimetic G3BP1 shows remarkably decreased RNA binding in dorsal root ganglion (DRG) neurons compared with wild-type and non-phosphorylatable G3BP1; combined with other studies, this suggests that CK2alpha-dependent G3BP1 phosphorylation on Ser 149 after axotomy releases axonal mRNAs for translation. Translation of axonal mRNAs encoding some injury-associated proteins is known to be increased with Ca(2+) elevations, and using a dual fluorescence recovery after photobleaching (FRAP) reporter assay for axonal translation, we see that translational specificity switches from injury-associated protein mRNA translation to CK2alpha translation with endoplasmic reticulum (ER) Ca(2+) release versus cytoplasmic Ca(2+) chelation. Our results point to axoplasmic Ca(2+) concentrations as a determinant for the temporal specificity of sequential translational activation of different axonal mRNAs as severed axons transition from injury to regenerative growth. |
