Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members

Andrew W. Hwang, Hanna Trzeciakiewicz, Dave Friedmann, Chao Xing Yuan, Ronen Marmorstein, Virginia M.Y. Lee, Todd J. Cohen

Research output: Contribution to journalArticle

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Abstract

Lysine acetylation has emerged as a dominant post-translational modification (PTM) regulating tau proteins in Alzheimer's disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule-binding region (MTBR), a region that is highly conserved among tau, MAP2, and MAP4 family members, implying that acetylation could represent a conserved regulatory mechanism for MAPs beyond tau. Here, we combined mass spectrometry, biochemical assays, and cell-based approaches to demonstrate that the tau family members MAP2 and MAP4 are also subject to reversible acetylation. We identify a cluster of lysines in the MAP2 and MAP4 MTBR that undergo CBP-catalyzed acetylation, many of which are conserved in tau. Similar to tau, MAP2 acetylation can occur in a cysteine-dependent auto-regulatory manner in the presence of acetyl-CoA. Furthermore, tubulin reduced MAP2 acetylation, suggesting tubulin binding dictates MAP acetylation status. Taken together, these results uncover a striking conservation of MAP2/Tau family post-translational modifications that could expand our understanding of the dynamic mechanisms regulating microtubules.

LanguageEnglish (US)
Article numbere0168913
JournalPloS one
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2016

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Acetylation
acetylation
Microtubules
microtubules
Lysine
lysine
post-translational modification
Post Translational Protein Processing
Tubulin
tubulin
Mass spectrometry
Mass Spectrometry
mass spectrometry
Tauopathies
tau Proteins
Acetyl Coenzyme A
Alzheimer disease
automobiles
Cysteine
cysteine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hwang, A. W., Trzeciakiewicz, H., Friedmann, D., Yuan, C. X., Marmorstein, R., Lee, V. M. Y., & Cohen, T. J. (2016). Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members. PloS one, 11(12), [e0168913]. https://doi.org/10.1371/journal.pone.0168913

Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members. / Hwang, Andrew W.; Trzeciakiewicz, Hanna; Friedmann, Dave; Yuan, Chao Xing; Marmorstein, Ronen; Lee, Virginia M.Y.; Cohen, Todd J.

In: PloS one, Vol. 11, No. 12, e0168913, 01.12.2016.

Research output: Contribution to journalArticle

Hwang, AW, Trzeciakiewicz, H, Friedmann, D, Yuan, CX, Marmorstein, R, Lee, VMY & Cohen, TJ 2016, 'Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members' PloS one, vol. 11, no. 12, e0168913. https://doi.org/10.1371/journal.pone.0168913
Hwang AW, Trzeciakiewicz H, Friedmann D, Yuan CX, Marmorstein R, Lee VMY et al. Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members. PloS one. 2016 Dec 1;11(12). e0168913. https://doi.org/10.1371/journal.pone.0168913
Hwang, Andrew W. ; Trzeciakiewicz, Hanna ; Friedmann, Dave ; Yuan, Chao Xing ; Marmorstein, Ronen ; Lee, Virginia M.Y. ; Cohen, Todd J. / Conserved lysine acetylation within the microtubule-binding domain regulates MAP2/tau family members. In: PloS one. 2016 ; Vol. 11, No. 12.
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