Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival
Yan Wang,
Evan G. Cameron,
Jinliang Li,
Travis L. Stiles,
Michael D. Kritzer,
Rahul Lodhavia,
Jonathan Hertz,
Tu Nguyen,
Michael S. Kapiloff,
Jeffrey L. Goldberg
Affiliations
Yan Wang
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States
Evan G. Cameron
Department of Ophthalmology, University of California, San Diego, CA 92093, United States
Jinliang Li
Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States
Travis L. Stiles
Department of Ophthalmology, University of California, San Diego, CA 92093, United States
Michael D. Kritzer
Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States
Rahul Lodhavia
Department of Ophthalmology, University of California, San Diego, CA 92093, United States
Jonathan Hertz
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States
Tu Nguyen
Department of Ophthalmology, University of California, San Diego, CA 92093, United States
Michael S. Kapiloff
Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States
Jeffrey L. Goldberg
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States
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-α (mAKAPα) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα 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 mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.
