Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases

被引:63
作者
Dagda, Ruben K. [1 ]
Das Banerjee, Tania [1 ]
机构
[1] Univ Nevada, Sch Med, Dept Pharmacol, Reno, NV 89557 USA
基金
美国国家卫生研究院;
关键词
A-kinase anchoring proteins; dendrites; mitochondrial dynamics; mitochondrial trafficking; neurodegeneration; protein kinase A; PROMOTES NEURITE OUTGROWTH; CAMP-RESPONSE ELEMENT; ANCHORING PROTEIN; RECEPTOR ACTIVATION; ALZHEIMERS-DISEASE; DOWN-REGULATION; MESSENGER-RNA; PKA; PHOSPHORYLATION; SUBUNIT;
D O I
10.1515/revneuro-2014-0085
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:359 / 370
页数:12
相关论文
共 85 条
[1]   Essential role of A-kinase anchor protein 121 for cAMP signaling to mitochondria [J].
Affaitati, A ;
Cardone, L ;
de Cristofaro, T ;
Carlucci, A ;
Ginsberg, MD ;
Varrone, S ;
Gottesman, ME ;
Avvedimento, EV ;
Feliciello, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) :4286-4294
[2]   cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons [J].
Aglah, C. ;
Gordon, T. ;
de Chaves, E. I. Posse .
NEUROPHARMACOLOGY, 2008, 55 (01) :8-17
[3]   Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics [J].
Alto, NM ;
Soderling, J ;
Scott, JD .
JOURNAL OF CELL BIOLOGY, 2002, 158 (04) :659-668
[4]   PKA phosphorylations on tau: Developmental studies in the mouse [J].
Andorfer, CA ;
Davies, P .
DEVELOPMENTAL NEUROSCIENCE, 2000, 22 (04) :303-309
[5]  
[Anonymous], COCHRANE DATABASE SY
[6]   High intracellular concentrations of amyloid-beta block nuclear translocation of phosphorylated CREB [J].
Arvanitis, D. N. ;
Ducatenzeiler, A. ;
Ou, J. N. ;
Grodstein, E. ;
Andrews, S. D. ;
Tendulkar, S. R. ;
Ribeiro-da-Silva, A. ;
Szyf, M. ;
Cuello, A. C. .
JOURNAL OF NEUROCHEMISTRY, 2007, 103 (01) :216-228
[7]   Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin [J].
Ashrafi, Ghazaleh ;
Schlehe, Julia S. ;
LaVoie, Matthew J. ;
Schwarz, Thomas L. .
JOURNAL OF CELL BIOLOGY, 2014, 206 (05) :655-670
[8]   Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons [J].
Berthet, Amandine ;
Margolis, Elyssa B. ;
Zhang, Jue ;
Hsieh, Ivy ;
Zhang, Jiasheng ;
Hnasko, Thomas S. ;
Ahmad, Jawad ;
Edwards, Robert H. ;
Sesaki, Hiromi ;
Huang, Eric J. ;
Nakamura, Ken .
JOURNAL OF NEUROSCIENCE, 2014, 34 (43) :14304-14317
[9]   Pharmacological management of Huntington's disease: An evidence-based review [J].
Bonelli, Raphael M. ;
Wenning, Gregor K. .
CURRENT PHARMACEUTICAL DESIGN, 2006, 12 (21) :2701-2720
[10]   Rab32 Modulates Apoptosis Onset and Mitochondria-associated Membrane (MAM) Properties [J].
Bui, Michael ;
Gilady, Susanna Y. ;
Fitzsimmons, Ross E. B. ;
Benson, Matthew D. ;
Lynes, Emily M. ;
Gesson, Kevin ;
Alto, Neal M. ;
Strack, Stefan ;
Scott, John D. ;
Simmen, Thomas .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (41) :31590-31602