PKCα integrates spatiotemporally distinct Ca and autocrine BDNF signaling to facilitate synaptic plasticity.

Authors:
Lesley A Colgan
Lesley A Colgan
University of Pittsburgh
Mo Hu
Mo Hu
Bangor University
United Kingdom
Paula Parra-Bueno
Paula Parra-Bueno
Duke University Medical Center
United States
Michael Leitges
Michael Leitges
University of Oslo
Germany
Ryohei Yasuda
Ryohei Yasuda
Howard Hughes Medical Institute

Nat Neurosci 2018 Aug 16;21(8):1027-1037. Epub 2018 Jul 16.

Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.

The protein kinase C (PKC) enzymes have long been established as critical for synaptic plasticity. However, it is unknown whether Ca-dependent PKC isozymes are activated in dendritic spines during plasticity and, if so, how this synaptic activity is encoded by PKC. Here, using newly developed, isozyme-specific sensors, we demonstrate that classical isozymes are activated to varying degrees and with distinct kinetics. PKCα is activated robustly and rapidly in stimulated spines and is the only isozyme required for structural plasticity. This specificity depends on a PDZ-binding motif present only in PKCα. The activation of PKCα during plasticity requires both NMDA receptor Ca flux and autocrine brain-derived neurotrophic factor (BDNF)-TrkB signaling, two pathways that differ vastly in their spatiotemporal scales of signaling. Our results suggest that, by integrating these signals, PKCα combines a measure of recent, nearby synaptic plasticity with local synaptic input, enabling complex cellular computations such as heterosynaptic facilitation of plasticity necessary for efficient hippocampus-dependent learning.

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PKC? integrates spatiotemporally distinct Ca2+ and autocrine BDNF signaling


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http://dx.doi.org/10.1038/s41593-018-0184-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100743PMC

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August 2018
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