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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Oct 6 2015

Fingerprint

Retinal Ganglion Cells
Scaffolds
Cyclic AMP
Protein Kinases
Muscle
Phosphotransferases
Muscles
Wounds and Injuries
Proteins
Optics
Muscle Proteins
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Neuroprotective Agents
Cell death
Optic Nerve Injuries
Nerve Crush
Neurons
Optic Nerve
Cells

Keywords

  • Axon growth
  • MAKAP
  • Optic nerve injury
  • Retinal ganglion cells
  • Survival

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival. / Wang, Yan; Cameron, Evan G.; Li, Jinliang; Stiles, Travis L.; Kritzer, Michael D.; Lodhavia, Rahul; Hertz, Jonathan; Nguyen, Tu; Kapiloff, Michael S; Goldberg, Jeffrey L.

In: EBioMedicine, 06.10.2015.

Research output: Contribution to journalArticle

Wang, Yan ; Cameron, Evan G. ; Li, Jinliang ; Stiles, Travis L. ; Kritzer, Michael D. ; Lodhavia, Rahul ; Hertz, Jonathan ; Nguyen, Tu ; Kapiloff, Michael S ; Goldberg, Jeffrey L. / Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival. In: EBioMedicine. 2015.
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AU - Li, Jinliang

AU - Stiles, Travis L.

AU - Kritzer, Michael D.

AU - Lodhavia, Rahul

AU - Hertz, Jonathan

AU - Nguyen, Tu

AU - Kapiloff, Michael S

AU - Goldberg, Jeffrey L.

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AB - 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.

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