Cytoskeletal signaling: Is memory encoded in microtubule lattices by CaMKII phosphorylation?

Travis J A Craddock, Jack A. Tuszynski, Stuart R Hameroff

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1002421
JournalPLoS Computational Biology
Volume8
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Calmodulin
Calcium-Calmodulin-Dependent Protein Kinases
Phosphorylation
Microtubules
microtubules
phosphorylation
phosphotransferases (kinases)
Phosphotransferases
Data storage equipment
Hexagon
Dependent
information processing
Neurons
calcium
Neuron
neurons
Information Processing
Automatic Data Processing
Encoding
protein

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Cytoskeletal signaling : Is memory encoded in microtubule lattices by CaMKII phosphorylation? / Craddock, Travis J A; Tuszynski, Jack A.; Hameroff, Stuart R.

In: PLoS Computational Biology, Vol. 8, No. 3, e1002421, 03.2012.

Research output: Contribution to journalArticle

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