Evolutionarily acquired activity-dependent transformation of the CaMKII holoenzyme

Tsujioka, S.; Sumino, A.; Nagasawa, Y.; Sumikama, T.; Flechsig, H.; Puppulin, L.; Tomita, T.; Baba, Y.; Kakuta, T.; Ogoshi, T.; Umeda, K.; Kodera, N.; Murakoshi, H.; Shibata, M.

doi:10.1101/2023.01.10.523378

bioRxiv · 10.1101/2023.01.10.523378

Evolutionarily acquired activity-dependent transformation of the CaMKII holoenzyme

Tsujioka, S.·Sumino, A.·Nagasawa, Y.·Sumikama, T.·Flechsig, H.·Puppulin, L.·Tomita, T.·Baba, Y.·Kakuta, T.·Ogoshi, T.·Umeda, K.·Kodera, N.·Murakoshi, H.·Shibata, M.

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Abstract

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has long been central in synaptic plasticity research. CaMKII is a dodecameric serine/threonine kinase that has been essentially conserved across metazoans for over a million years. While the mechanisms of CaMKII activation are well studied, its "behavior" at the molecular level has remained unobserved. Here, high-speed atomic force microscopy was used to visualize the activity-dependent structural dynamics of rat/hydra/C. elegans CaMKII in various states at nanometer resolution. Among the species, rat CaMKII underwent internal kinase domain aggregation in an activity-dependent manner and showed a higher tolerance to dephosphorylation by phosphatase. Our findings suggest that mammalian CaMKII has evolutionarily acquired a new structural form and a tolerance to phosphatase to maintain robust CaMKII activity for proper neuronal function. One-Sentence SummaryHigh-speed atomic force microscopy reveals the activity-dependent structural dynamics of rat/hydra/C. elegans CaMKII

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Tsujioka, S., Sumino, A., Nagasawa, Y., Sumikama, T., Flechsig, H., Puppulin, L., Tomita, T., Baba, Y., Kakuta, T., Ogoshi, T., Umeda, K., Kodera, N., Murakoshi, H., Shibata, M.. 2023-01-10. Evolutionarily acquired activity-dependent transformation of the CaMKII holoenzyme. https://doi.org/10.1101/2023.01.10.523378

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