Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-12-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415301857 |
| _version_ | 1819205118668570624 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T04:46:37Z |
| format | Article |
| id | doaj.art-1edf7cef646c44d28b418c20d2ebdff0 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-23T04:46:37Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-1edf7cef646c44d28b418c20d2ebdff02022-12-21T17:59:37ZengElsevierEBioMedicine2352-39642015-12-012121880188710.1016/j.ebiom.2015.10.025Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated SurvivalYan Wang0Evan G. Cameron1Jinliang Li2Travis L. Stiles3Michael D. Kritzer4Rahul Lodhavia5Jonathan Hertz6Tu Nguyen7Michael S. Kapiloff8Jeffrey L. Goldberg9Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United StatesDepartment of Ophthalmology, University of California, San Diego, CA 92093, United StatesDepartment of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United StatesDepartment of Ophthalmology, University of California, San Diego, CA 92093, United StatesDepartment of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United StatesDepartment of Ophthalmology, University of California, San Diego, CA 92093, United StatesBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United StatesDepartment of Ophthalmology, University of California, San Diego, CA 92093, United StatesDepartment of Pediatrics, Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, United StatesBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United StatesNeurotrophic 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.http://www.sciencedirect.com/science/article/pii/S2352396415301857mAKAPRetinal ganglion cellsSurvivalAxon growthOptic nerve injury |
| spellingShingle | 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 Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival EBioMedicine mAKAP Retinal ganglion cells Survival Axon growth Optic nerve injury |
| title | Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival |
| title_full | Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival |
| title_fullStr | Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival |
| title_full_unstemmed | Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival |
| title_short | Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival |
| title_sort | muscle a kinase anchoring protein α is an injury specific signaling scaffold required for neurotrophic and cyclic adenosine monophosphate mediated survival |
| topic | mAKAP Retinal ganglion cells Survival Axon growth Optic nerve injury |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415301857 |
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