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MAP2-mediated in vitro interactions of brain microtubules and their modulation by cAMP

J F Leterrier1, M Kurachi, T Tashiro

  • 1Department of Neurosciences, UMR 6187 CNRS, P.B.S., Poitiers University, 40 Avenue du, Recteur Pineau, 86022, Poitiers Cedex, France. jean.francois.leterrier@univ-poitiers.fr

European Biophysics Journal : EBJ
|November 15, 2008
PubMed

Insights

Cyclic AMP (cAMP) influences microtubule (MT) interactions through microtubule-associated protein 2 (MAP2). It affects MT bundling via phosphorylation and phosphorylation-independent mechanisms, impacting neuronal structure.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • Microtubule-associated proteins (MAPs) regulate microtubule (MT) organization, including bundling and cross-bridging.
  • MAPs' MT bundling function is attributed to their MT-binding domain, modulated by the projection domain.
  • The role of cyclic AMP (cAMP) in modulating these interactions is not fully understood.

Purpose of the Study:

  • To investigate the effect of cAMP on microtubule (MT) viscoelastic properties and interactions.
  • To elucidate the mechanisms by which cAMP modulates microtubule-associated protein 2 (MAP2)-mediated MT interactions.

Main Methods:

  • Analysis of viscoelastic properties of microtubule (MT) suspensions.
  • Experiments conducted in the presence and absence of cyclic AMP (cAMP).
  • Investigation of cAMP-dependent protein kinase A (PKA) interactions with MAP2.

Main Results:

  • Cyclic AMP (cAMP) modulates interactions between microtubule (MT) polymers involving MAP2.
  • Two distinct cAMP mechanisms identified: phosphorylation of MT proteins by PKA and direct cAMP binding to PKA's RII subunit.
  • These mechanisms affect MT-MT interactions in both phosphorylation-dependent and -independent manners.

Conclusions:

  • The complex of PKA with MAP2's projection domain plays a role in MT-MT interactions.
  • cAMP directly influences the density and bundling of MT arrays within neuronal dendrites.
  • Findings suggest cAMP is a key regulator of microtubule organization in neurons.

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