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

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...

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Autores principales: Travis J A Craddock, Jack A Tuszynski, Stuart Hameroff
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:f844c05f5346481dbd8e7cd4854440642021-11-18T05:51:31ZCytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?1553-734X1553-735810.1371/journal.pcbi.1002421https://doaj.org/article/f844c05f5346481dbd8e7cd4854440642012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412364/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Memory 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.Travis J A CraddockJack A TuszynskiStuart HameroffPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 3, p e1002421 (2012)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Travis J A Craddock
Jack A Tuszynski
Stuart Hameroff
Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
description 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.
format article
author Travis J A Craddock
Jack A Tuszynski
Stuart Hameroff
author_facet Travis J A Craddock
Jack A Tuszynski
Stuart Hameroff
author_sort Travis J A Craddock
title Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
title_short Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
title_full Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
title_fullStr Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
title_full_unstemmed Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation?
title_sort cytoskeletal signaling: is memory encoded in microtubule lattices by camkii phosphorylation?
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f844c05f5346481dbd8e7cd485444064
work_keys_str_mv AT travisjacraddock cytoskeletalsignalingismemoryencodedinmicrotubulelatticesbycamkiiphosphorylation
AT jackatuszynski cytoskeletalsignalingismemoryencodedinmicrotubulelatticesbycamkiiphosphorylation
AT stuarthameroff cytoskeletalsignalingismemoryencodedinmicrotubulelatticesbycamkiiphosphorylation
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