Abstract
In neurons, enhanced protein kinase A (PKA) signaling elevates synaptic plasticity, promotes neuronal development, and increases dopamine synthesis. By contrast, a decline in PKA signaling contributes to the etiology of several brain degenerative diseases, including Alzheimer’s disease and Parkinson’s disease, suggesting that PKA predominantly plays a neuroprotective role. A-kinase anchoring proteins (AKAPs) are large multidomain scaffold proteins that target PKA and other signaling molecules to distinct subcellular sites to strategically localize PKA signaling at dendrites, dendritic spines, cytosol, and axons. PKA can be recruited to the outer mitochondrial membrane by associating with three different AKAPs to regulate mitochondrial dynamics, structure, mitochondrial respiration, trafficking, dendrite morphology, and neuronal survival. In this review, we survey the myriad of essential neuronal functions modulated by PKA but place a special emphasis on mitochondrially localized PKA. Finally, we offer an updated overview of how loss of PKA signaling contributes to the etiology of several brain degenerative diseases.
About the authors
Ruben K. Dagda, PhD, received his doctoral training at the University of Iowa in 2006 and his postdoctoral training at the University of Pittsburgh School of Medicine (2006–2012). As an assistant professor at the University of Nevada School of Medicine, he is committed to the training and education of undergraduate, graduate, and postdoc students in his lab. He is a faculty member of the Molecular Biosciences and the Cellular Molecular Pharmacology and Physiology graduate programs. He is currently investigating the molecular mechanisms that lead to mitochondrial dysfunction and loss of neurites in cell culture, tissue, and animal models of Parkinson’s disease. He has authored in multiple research manuscripts and review articles in the areas of toxicology, toxinology, mitochondrial function, and neurobiology.
Tania Das Banerjee, PhD, MPH, earned her PhD degree in Neuroscience from SUNY Upstate Medical University at Syracuse, New York, in 2010. She then went on to complete her Master’s in Public Health degree in Environmental and Molecular Toxicology from Columbia University in 2012. Currently, she is a postdoctoral fellow in the Department of Pharmacology at the University of Nevada Reno. Dr. Das Banerjee’s research focuses on the molecular analysis of pathological mechanisms in neurodegenerative diseases. Her work aims to understand basic properties of dendritic arborization and its relation to mitochondrial function that are relevant in normal brain function and neurodegeneration.
Acknowledgments
This review was supported a COBRE grant in ‘Cell Signaling across Cell Membranes’ by the National Institutes of Health (grant no. GM103554).
Conflicts of interest: The authors have no conflicts of interest to declare.
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