title: Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival.
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-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.
authors: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Department of Ophthalmology, University of California, San Diego, CA 92093, United States.
authors: Yan
authors: Y
authors: Wang
authors: Department of Ophthalmology, University of California, San Diego, CA 92093, United States; Byers Eye Institute, Stanford University, Palo Alto, CA 94303, United States.
authors: Evan G
authors: EG
authors: Cameron
authors: Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States; Department of Medicine, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States.
authors: Jinliang
authors: J
authors: Li
authors: Department of Ophthalmology, University of California, San Diego, CA 92093, United States.
authors: Travis L
authors: TL
authors: Stiles
authors: Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States; Department of Medicine, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States.
authors: Michael D
authors: MD
authors: Kritzer
authors: Department of Ophthalmology, University of California, San Diego, CA 92093, United States.
authors: Rahul
authors: R
authors: Lodhavia
authors: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
authors: Jonathan
authors: J
authors: Hertz
authors: Department of Ophthalmology, University of California, San Diego, CA 92093, United States.
authors: Tu
authors: T
authors: Nguyen
authors: Department of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States; Department of Medicine, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United States.
authors: Michael S
authors: MS
authors: Kapiloff
authors: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Department of Ophthalmology, University of California, San Diego, CA 92093, United States; Byers Eye Institute, Stanford University, Palo Alto, CA 94303, United States.
authors: Jeffrey L
authors: JL
authors: Goldberg
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; C484293:Akap6 protein, rat; D009414:Nerve Growth Factors; D000242:Cyclic AMP
keywords: Axon growth; Optic nerve injury; Retinal ganglion cells; Survival; mAKAP