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Inhibition of neuronal calcium oscillations by cell surface APP phosphorylated on T668
- Source :
- Neurobiology of Aging. 32:2308-2313
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Adenoviral expression of human APP (hAPP), but not of hAPP deleted from its C-terminal intracellular domain, in rat cortical neurons abolishes spontaneous synchronous calcium oscillations. The intracellular domain of APP695 contains several residues that can be phosphorylated. Contrary to non-neuronal cells, a very high phosphorylation of APP on T668 is observed in neurons, which is mediated by JNK, GSK3 and Cdk5 protein kinases. JNK activity, modulated by GSK3, enhances the traffic of phosphorylated APP to nerve terminals, contrary to Cdk5. Here we show that inhibition of GSK3 and JNK restores calcium oscillations in an hAPP expressing neuronal network, whereas inhibition of Cdk5 does not. Expression of mutant hAPPT668A does not inhibit calcium oscillations, and the proportion of hAPPT668A at the plasma membrane is reduced by more than 50%. Altogether, these results indicate that the intracellular domain of APP is needed to inhibit neuronal calcium oscillations because GSK3/JNK phosphorylation of T668 controls APP trafficking at the plasma membrane.
- Subjects :
- Threonine
Aging
Mutant
Cell
chemistry.chemical_element
macromolecular substances
Biology
Calcium
Amyloid beta-Protein Precursor
medicine
Biological neural network
Animals
Humans
Calcium Signaling
Phosphorylation
Rats, Wistar
Cells, Cultured
Neurons
Kinase
General Neuroscience
Cyclin-dependent kinase 5
Membrane Proteins
Neural Inhibition
Intracellular Membranes
Cortical neurons
Protein Structure, Tertiary
Rats
Cell biology
Protein Transport
medicine.anatomical_structure
nervous system
chemistry
Mutation
Neurology (clinical)
Geriatrics and Gerontology
Developmental Biology
Subjects
Details
- ISSN :
- 01974580
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi.dedup.....2a04c512db8e1d4ef0d3e10354a934e8