Muscle A-Kinase Anchoring Protein-a is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival. EBioMedicine Wang, Y., Cameron, E. G., Li, J., Stiles, T. L., Kritzer, M. D., Lodhavia, R., Hertz, J., Nguyen, T., Kapiloff, M. S., Goldberg, J. L. 2015; 2 (12): 1880-1887

Abstract

Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs) after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-a (mAKAPa) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPa early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPa in the adult increased RGC death after optic nerve crush. Importantly, mAKAPa was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPa as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.

View details for DOI 10.1016/j.ebiom.2015.10.025

View details for PubMedID 26844267