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Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions.

ABSTRACT: CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca(2+) (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement for nucleotide binding but not auto-phosphorylation also for extra-synaptic clustering within neurons. These results clarify a previously apparent paradox in the nucleotide and phosphorylation requirement of aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T-site interaction.

SUBMITTER: Vest RS

PROVIDER: S-EPMC2790910 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions.

Vest Rebekah S RS O'Leary Heather H Bayer K Ulrich KU

FEBS letters 20091017 22

CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca(2+) (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement ...[more]

PMID: 19840793

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