PKMζ is necessary and sufficient for synaptic clustering of PSD-95
✍ Scribed by Charles Y. Shao; Rachna Sondhi; Paula S. van de Nes; Todd Charlton Sacktor
- Book ID
- 102851853
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 958 KB
- Volume
- 22
- Category
- Article
- ISSN
- 1050-9631
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✦ Synopsis
Abstract
The persistent activity of protein kinase Mzeta (PKMζ), a brain‐specific, constitutively active protein kinase C isoform, maintains synaptic long‐term potentiation (LTP). Structural remodeling of the postsynaptic density is believed to contribute to the expression of LTP. We therefore examined the role of PKMζ in reconfiguring PSD‐95, the major postsynaptic scaffolding protein at excitatory synapses. In primary cultures of hippocampal neurons, PKMζ activity was critical for increasing the size of PSD‐95 clusters during chemical LTP (cLTP). Increasing PKMζ activity by overexpressing the kinase in hippocampal neurons was sufficient to increase PSD‐95 cluster size, spine size, and postsynaptic AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMζ did not increase PSD‐95 clustering, and applications of the ζ‐pseudosubstrate inhibitor ZIP reversed the PKMζ‐mediated increases in PSD‐95 clustering, indicating that the activity of PKMζ is necessary to induce and maintain the increased size of PSD‐95 clusters. Thus the persistent activity of PKMζ is both necessary and sufficient for maintaining increases of PSD‐95 clusters, providing a unified mechanism for long‐term functional and structural modifications of synapses. © 2011 Wiley Periodicals, Inc.