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

Benoit Roger, Jawdat Al-Bassam, Leif Dehmelt, Ronald A. Milligan, Shelley Halpain

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)363-371
Number of pages9
JournalCurrent Biology
Volume14
Issue number5
DOIs
StatePublished - Mar 9 2004
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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    Roger, B., Al-Bassam, J., Dehmelt, L., Milligan, R. A., & Halpain, S. (2004). MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain. Current Biology, 14(5), 363-371. https://doi.org/10.1016/j.cub.2004.01.058