Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation?

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 sets of six CaMKII kinase domains phosphorylate hexagonal MT lattice neighborhoods collectively, e.g. conveying synaptic information as ordered arrays of six “bits”, and thus “bytes”, with 64 to 5,281 possible bit states per CaMKII-MT byte. Signaling and encoding in MTs and other cytoskeletal structures offer rapid, robust solid-state information processing which may reflect a general code for MT-based memory and information processing within neurons and other eukaryotic cells.

The Sixth Sense-Emotional Contagion; Review of Biophysical Mechanisms Influencing Information Transfer in Groups

“…What was also interesting was their mention that quantum coherence may exist although they did not consider it a prerequisite for their hypothesis, quantum coherence effects may tie in with the initial focus of attention effect noted between participants in crowd formation. This effect was proposed in biological systems [207]- [210].…”

Biological Quasicrystals and the Golden Mean: Relevance to Quantum Computation

“…The hexagonal sets of kinase domains seem possibly positioned for interaction with the hexagonal array of tubulin subunits within a microtubule. Thus phosphorylation of tubulin subunits offers the potential for vast storage of information (Craddock et al, 2012). Other posttranslational modification of microtubules may encode information which can then be "read" by microtubule-associated proteins (Verhey and Gaertig, 2007).…”

Quantum Logic of the Unconscious and Schizophrenia

“…Potential computational modes for MTs and actin filaments are emerging with two main quantum models for MT information processing having been proposed: the "doublewell" potential, advanced by Craddock and Tuszynski (Craddock, 2009;2012) and "Orchestrated Objective Reduction" (Orch-OR), put forward by Penrose and Hameroff (Hameroff, 1996;Penrose, 2011).…”