Dystrophin is a microtubule-associated protein.
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 K(d) of 0.66 microM, a stoichiometry of 1 Dp260/1.4 tubulin heterodimer at saturation, and stabilizes MTs from cold-induced depolymerization. Finally, alpha- and beta-tubulin expression is increased approximately 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.
Prins
Kurt W
KW
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Humston
Jill L
JL
Mehta
Amisha
A
Tate
Victoria
V
Ralston
Evelyn
E
Ervasti
James M
JM
D000818:Animals; D016189:Dystrophin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D016189:Dystrophin; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms