Calmodulin binds to a tubulin binding site of the microtubule-associated protein tau.
Previous studies have demonstrated that the microtubule-associated proteins MAP-2 and tau interact selectively with common binding domains on tubulin defined by the low-homology segments alpha (430-441) and beta (422-434). It has been also indicated that the synthetic peptide VRSKIGSTENLKHQPGGG corresponding to the first tau repetitive sequence represents a tubulin binding domain on tau. The present studies show that the calcium-binding protein calmodulin interacts with a tubulin binding site on tau defined by the second repetitive sequence VTSKCGSLGNIHHKPGGG. It was shown that both tubulin and calmodulin bind to tau peptide-Sepharose affinity column. Binding of calmodulin occurs in the presence of 1 mM Ca 2+ and it can be eluted from the column with 4 mM EGTA. These findings provide new insights into the regulation of microtubule assembly, since Ca2+/calmodulin inhibition of tubulin polymerization into microtubules could be mediated by the direct binding of calmodulin to tau, thus preventing the interaction of this latter protein with tubulin.
Padilla
R
R
Centro de Bíologia Molecular, Universidad Autónoma, Madrid, Spain.
Maccioni
R B
RB
Avila
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins
D002147:Calmodulin; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins; D002118:Calcium