TrkB and Protein Kinase M ζ Regulate Synaptic Localization of PSD-95 in Developing Cortex
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Yoshii-2011-Aug-TrkB and Protein Kinase.pdf
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Author(s)
Yoshii, Akira
Murata, Yasunobu
Kim, Jihye
Shokat, Kevan M.
Constantine-Paton, Martha
Zhang, Chao, Ph. D. Massachusetts Institute of Technology
Date Issued
June 2011
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Yoshii, A. et al. “TrkB and Protein Kinase M ζ Regulate Synaptic Localization of PSD-95 in Developing Cortex.” Journal of Neuroscience 31.33 (2011): 11894–11904. Web.
Version
Final published version
Abstract
Postsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We showed previously that the PI3 kinase–Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also, PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely, signaling through phospholipase Cγ and the brain-specific PKC variant protein kinase M ζ (PKMζ). We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by overexpressing ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as aging brains.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1523/jneurosci.2190-11.2011
