New Paper

Arjen van Ooyen a.van.ooyen at nih.knaw.nl
Fri Nov 30 07:37:53 EST 2001


A Computational Model of Dendrite Elongation and
Branching Based on MAP2 Phosphorylation

by  T. A. Hely, B. P. Graham & A. van Ooyen

J. Theor. Biol. (2001) 210: 375-384.

The full paper can be downloaded from
http://www.anc.ed.ac.uk/~arjen/papers/map_abstract.html


Abstract

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.

--
Arjen van Ooyen, Netherlands Institute for Brain Research,
Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands.
email: A.van.Ooyen at nih.knaw.nl
website: http://www.anc.ed.ac.uk/~arjen
phone: +31.20.5665483  fax: +31.20.6961006




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