Transitions in microtubule C-termini conformations as a possible dendritic signaling phenomenon
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We model the dynamical states of the C-termini of tubulin dimers that comprise neuronal microtubules. We use molecular dynamics and other computational tools to explore the time-dependent behavior of conformational states of a C-terminus of tubulin within a microtubule and assume that each C-terminus interacts via screened Coulomb forces with the surface of a tubulin dimer, with neighboring C-termini and also with any adjacent microtubule-associated protein 2 (MAP2). Each C-terminus can either bind to the tubulin surface via one of the several positively charged regions or can be allowed to explore the space available in the solution surrounding the dimer. We find that the preferential orientation of each C-terminus is away from the tubulin surface but binding to the surface may also take place, albeit at a lower probability. The results of our model suggest that perturbations generated by the C-termini interactions with counterions surrounding a MAP2 may propagate over distances greater than those between adjacent microtubules. Thus, the MAP2 structure is able to act as a kind of biological wire (or a cable) transmitting local electrostatic perturbations resulting in ionic concentration gradients from one microtubule to another. We briefly discuss the implications the current dynamic modeling may have on synaptic activation and potentiation.
KeywordsNeuron Synapse MAP Ionic wave Protein filament Electrostatic interaction
This research was supported by grants from NSERC, MITACS-MMPD and the YeTaDel Foundation. We thank Mr. Eric Carpenter for assistance in computational work. Discussions with Dr. Dan Sackett of NIH are gratefully acknowledged.
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