A computational model of dendrite elongation and branching based on MAP2 phosphorylation.
We introduce a new computational model of dendritic development in neurons. In contrast to previous models, our model explicitly includes cellular mechanisms involved in dendritic development. It is based on recent experimental data which indicates that the phosphorylation state of microtubule-associated protein 2 (MAP2) may play a key role in controlling dendritic elongation and branching (Audesirk et al., 1997). Dephosphorylated MAP2 favours elongation by promoting microtubule polymerization and bundling, whilst branching is more likely to occur when MAP2 is phosphorylated and microtubules are spaced apart. In the model, the rate of elongation and branching is directly determined by the ratio of phosphorylated to dephosphorylated MAP2. This is regulated by calmodulin-dependent protein kinase II (CaMKII) and calcineurin, which are both dependent on the intracellular calcium concentration. Results from computer simulations of the model suggest that the wide variety of branching patterns observed among different cell types may be generated by the same underlying mechanisms and that elongation and branching are not necessarily independent processes. The model predicts how the branching pattern will change following manipulations with calcium, CaMKII and MAP2 phosphorylation.
Hely
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Division of Informatics, Institute for Adaptive and Neural Computation, University of Edinburgh, 5 Forrest Hill, Edinburgh, Scotland, EH1 2QL, UK. tim@anc.ed.ac.uk
Graham
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B
Ooyen
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D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003198:Computer Simulation; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008959:Models, Neurological; D010766:Phosphorylation
D008869:Microtubule-Associated Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D002118:Calcium