MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain

Curr Biol. 2004 Mar 9;14(5):363-71. doi: 10.1016/j.cub.2004.01.058.


Background: MAP2 and tau are abundant microtubule-associated proteins (MAPs) in neurons. The development of neuronal dendrites and axons requires a dynamic interaction between microtubules and actin filaments. MAPs represent good candidates to mediate such interactions. Although MAP2c and tau have similar, well-characterized microtubule binding activities, their actin interaction is poorly understood.

Results: Here, we show by using a cosedimentation assay that MAP2c binds F-actin. Upon actin binding, MAP2c organizes F-actin into closely packed actin bundles. Moreover, we show by using a deletion approach that MAP2c's microtubule binding domain (MTBD) is both necessary and sufficient for both F-actin binding and bundling activities. Surprisingly, even though the MAP2 and tau MTBDs share high sequence homology and possess similar microtubule binding activities, tau is unable to bind or bundle F-actin. Furthermore, experiments with chimeric proteins demonstrate that the actin binding activity fully correlates with the ability to promote neurite initiation in neuroblastoma cells.

Conclusions: These results provide the first demonstration that the MAP2c and tau MTBD domains exhibit distinct properties, diverging in actin binding and neurite initiation activities. These results implicate a novel actin function for MAP2c in neuronal morphogenesis and furthermore suggest that actin interactions could contribute to functional differences between MAP2 and tau in neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Binding Sites / physiology
  • Cells, Cultured
  • Centrifugation
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Immunohistochemistry
  • Microscopy, Electron
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Morphogenesis / physiology
  • Neurons / metabolism*
  • Neurons / physiology
  • Recombinant Fusion Proteins / metabolism
  • tau Proteins / metabolism*


  • Actins
  • DNA Primers
  • Microtubule-Associated Proteins
  • Recombinant Fusion Proteins
  • tau Proteins