cytoskeletal signaling is memory encoded in microtubule lattices by camkii phosphorylation在微管细胞骨架信号是记忆编码格camkii磷酸化.pdfVIP

Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation? 1 1,2 3 Travis J. A. Craddock *, Jack A. Tuszynski , Stuart Hameroff 1 Department of Physics, University of Alberta, Edmonton, Canada, 2 Department of Experimental Oncology, Cross Cancer Institute, Edmonton, Canada, 3 Departments of Anesthesiology and Psychology, Center for Consciousness Studies, University of Arizona, Tucson, Arizona, United States of America Abstract Memory is attributed to strengthened synaptic connections among particular brain neurons, yet synaptic membrane components are transient, whereas memories can endure. This suggests synaptic information is encoded and ‘hard-wired’ elsewhere, e.g. at molecular levels within the post-synaptic neuron. In long-term potentiation (LTP), a cellular and molecular model for memory, post-synaptic calcium ion (Ca2+) flux activates the hexagonal Ca2+-calmodulin dependent kinase II (CaMKII), a dodacameric holoenzyme containing 2 hexagonal sets of 6 kinase domains. Each kinase domain can either phosphorylate substrate proteins, or not (i.e. encoding one bit). Thus each set of extended CaMKII kinases can potentially encode synaptic Ca2+ information via phosphorylation as ordered arrays of binary ‘bits’. Candidate sites for CaMKII phosphorylation-encoded molecular memory include microtubules (MTs), cylindrical organelles whose surfaces represent a regular lattice with a pattern of hexagonal polymers of the protein tubulin. Using molecular mechanics modeling and electrostatic profiling, we find that spatial dimensions and geometry of the extended CaMKII kinase domains precisely match those of MT hexagonal lattices. This suggests