isolation-ca1-nuclear-enriched-fractions-from-hippocampal-slices-to

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Studying activity dependent protein expression, subcellular translocation, or phosphorylation is essential to understand the underlying cellular ...

Leibniz Institute for Neurobiology

The activation of N-methyl-D-aspartate-receptors (NMDARs) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration. At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus. In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus. Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine-180 by ERK1/2. Long-distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament α-internexin hinders dephosphorylation of the Jacob/ERK complex during nuclear transit. In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity.

Article	Year
Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus. Cell\| PubMed ID: 23452857	2013
When synaptic proteins meet the genome: transcriptional regulation in cell death and plasticity by the synapto-nuclear messenger Jacob. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology\| PubMed ID: 24317321	2014

Sujoy Bera

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