Dystrophin is a microtubule-associated protein

Kurt W. Prins, Jill L. Humston, Amisha Mehta, Victoria Tate, Evelyn Ralston, James M. Ervasti

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Cytolinkers are giant proteins that can stabilize cells by linking actin filaments, intermediate filaments, and microtubules (MTs) to transmembrane complexes. Dystrophin is functionally similar to cytolinkers, as it links the multiple components of the cellular cytoskeleton to the transmembrane dystroglycan complex. Although no direct link between dystrophin and MTs has been documented, costamere-associated MTs are disrupted when dystrophin is absent. Using tissue-based cosedimentation assays on mice expressing endogenous dystrophin or truncated transgene products, we find that constructs harboring spectrinlike repeat 24 through the first third of the WW domain cosediment with MTs. Purified Dp260, a truncated isoform of dystrophin, bound MTs with a Kd of 0.66 μM, a stoichiometry of 1 Dp260/1.4 tubulin heterodimer at saturation, and stabilizes MTs from cold-induced depolymerization. Finally, α- and β-tubulin expression is increased ∼2.5-fold in mdx skeletal muscle without altering the tubulin-MT equilibrium. Collectively, these data suggest dystrophin directly organizes and/or stabilizes costameric MTs and classifies dystrophin as a cytolinker in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)363-369
Number of pages7
JournalJournal of Cell Biology
Volume186
Issue number3
DOIs
StatePublished - Aug 10 2009

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Dystrophin
Microtubule-Associated Proteins
Microtubules
Tubulin
Costameres
Plakins
Skeletal Muscle
Dystroglycans
Intermediate Filaments
Cytoskeleton
Actin Cytoskeleton
Transgenes
Protein Isoforms

Cite this

Dystrophin is a microtubule-associated protein. / Prins, Kurt W.; Humston, Jill L.; Mehta, Amisha; Tate, Victoria; Ralston, Evelyn; Ervasti, James M.

In: Journal of Cell Biology, Vol. 186, No. 3, 10.08.2009, p. 363-369.

Research output: Contribution to journalArticle

Prins, KW, Humston, JL, Mehta, A, Tate, V, Ralston, E & Ervasti, JM 2009, 'Dystrophin is a microtubule-associated protein', Journal of Cell Biology, vol. 186, no. 3, pp. 363-369. https://doi.org/10.1083/jcb.200905048
Prins, Kurt W. ; Humston, Jill L. ; Mehta, Amisha ; Tate, Victoria ; Ralston, Evelyn ; Ervasti, James M. / Dystrophin is a microtubule-associated protein. In: Journal of Cell Biology. 2009 ; Vol. 186, No. 3. pp. 363-369.
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