A structural mechanism for maintaining the ‘on‐state’ of the CaMKII memory switch in the post‐synaptic density
Open Access
- 3 June 2007
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 103 (1), 357-364
- https://doi.org/10.1111/j.1471-4159.2007.04744.x
Abstract
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by Ca2+ entry into neurons. Autophosphorylation of T286 is of special importance because it makes the enzyme active in the absence of Ca2+, providing a biochemical memory that is critical for plasticity. To understand the factors controlling the duration of this state of CaMKII, we studied dephosphorylation of CaMKII in the post-synaptic density (PSD), a structure that defines a neuronal subcompartment critical for plasticity. We found that PSD-resident PP1 can dephosphorylate many sites on CaMKII, but not the T286 site that produces Ca2+-independent activity. This, together with previous work showing that soluble PP2A cannot dephosphorylate PSD CaMKII, provides a novel explanation for the in vivo persistence of T286 phosphorylation: after activated CaMKII translocates from the cytoplasm to the PSD, structural constraints prevent phosphatases from dephosphorylating T286. These results also suggest that the PSD is more than a simple scaffold for synaptic proteins; it may act to regulate the activity of proteins by positioning them in orientations that either prevent or favor specific biochemical reactions.Keywords
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