A direct interaction between leucine-rich repeat kinase 2 and specific β-Tubulin isoforms regulates tubulin acetylation

Bernard M H Law, Victoria A. Spain, Veronica H L Leinster, Ruth Chia, Alexandra Beilina, Hyun J. Cho, Jean Marc Taymans, Mary K. Urban, Rosa M. Sancho, Marian Blanca Ramírez, Saskia Biskup, Veerle Baekelandt, Huaibin Cai, Mark R. Cookson, Daniel C. Berwick, Kirsten Harvey

Research output: Contribution to journalArticle

Abstract

Background: Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) cause Parkinson disease. Results: LRRK2 binds directly to three -tubulin isoforms at the luminal face of microtubules and suppresses α-tubulin acetylation. Interaction is weakened by the R1441G LRRK2 GTPase domain mutant. Conclusion: LRRK2 modulates microtubule stability. Significance: Deregulation of microtubule-dependent processes likely contribute to neurodegeneration in Parkinson disease.

Original languageEnglish (US)
Pages (from-to)895-908
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number2
DOIs
StatePublished - Jan 10 2014
Externally publishedYes

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Acetylation
Tubulin
Leucine
Protein Isoforms
Phosphotransferases
Microtubules
Parkinson Disease
Gene encoding
Deregulation
GTP Phosphohydrolases
Mutation
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Law, B. M. H., Spain, V. A., Leinster, V. H. L., Chia, R., Beilina, A., Cho, H. J., ... Harvey, K. (2014). A direct interaction between leucine-rich repeat kinase 2 and specific β-Tubulin isoforms regulates tubulin acetylation. Journal of Biological Chemistry, 289(2), 895-908. https://doi.org/10.1074/jbc.M113.507913

A direct interaction between leucine-rich repeat kinase 2 and specific β-Tubulin isoforms regulates tubulin acetylation. / Law, Bernard M H; Spain, Victoria A.; Leinster, Veronica H L; Chia, Ruth; Beilina, Alexandra; Cho, Hyun J.; Taymans, Jean Marc; Urban, Mary K.; Sancho, Rosa M.; Ramírez, Marian Blanca; Biskup, Saskia; Baekelandt, Veerle; Cai, Huaibin; Cookson, Mark R.; Berwick, Daniel C.; Harvey, Kirsten.

In: Journal of Biological Chemistry, Vol. 289, No. 2, 10.01.2014, p. 895-908.

Research output: Contribution to journalArticle

Law, BMH, Spain, VA, Leinster, VHL, Chia, R, Beilina, A, Cho, HJ, Taymans, JM, Urban, MK, Sancho, RM, Ramírez, MB, Biskup, S, Baekelandt, V, Cai, H, Cookson, MR, Berwick, DC & Harvey, K 2014, 'A direct interaction between leucine-rich repeat kinase 2 and specific β-Tubulin isoforms regulates tubulin acetylation', Journal of Biological Chemistry, vol. 289, no. 2, pp. 895-908. https://doi.org/10.1074/jbc.M113.507913
Law, Bernard M H ; Spain, Victoria A. ; Leinster, Veronica H L ; Chia, Ruth ; Beilina, Alexandra ; Cho, Hyun J. ; Taymans, Jean Marc ; Urban, Mary K. ; Sancho, Rosa M. ; Ramírez, Marian Blanca ; Biskup, Saskia ; Baekelandt, Veerle ; Cai, Huaibin ; Cookson, Mark R. ; Berwick, Daniel C. ; Harvey, Kirsten. / A direct interaction between leucine-rich repeat kinase 2 and specific β-Tubulin isoforms regulates tubulin acetylation. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 2. pp. 895-908.
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