The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation.
The FK506 binding protein FKBP52 belongs to the large family of immunophilins and is known as a steroid receptor-associated protein. Previous data suggest that FKBP52 is associated with the motor protein dynein and with the cytoskeleton during mitosis. Here we demonstrate a specific and direct interaction between FKBP52 and tubulin. The region of FKBP52 located between aa 267 and 400, which includes the tetratricopeptide repeat domain, is required for tubulin binding. We provide evidence that FKBP52 prevents tubulin polymerization and that an 84 residue sequence located in the C-terminal part of the molecule (aa 375-458) is necessary and sufficient for its microtubule depolymerization activity. In colocalization experiments in PC12 cells, FKBP52 is associated with tubulin in motile cellular compartments. Furthermore, we suggest that, by using siRNA, a decrease of FKBP52 expression in PC12 cells may lead to differentiated cell phenotype characterized by neurite extensions. Collectively, our data define an unexpected property of FKBP52 as a novel regulator of microtubule dynamics. The possible role of microtubule formation and tubulin binding of other immunophilins such as FKBP12 and FKBP51 is discussed.
Chambraud
Béatrice
B
INSERM, Unité mixte de recherche 788, Université ParisXI, 80 rue du Général leclerc, Kremlin Bicêtre 94276, France.
Belabes
Hamida
H
Fontaine-Lenoir
Virginie
V
Fellous
Arlette
A
Baulieu
Etienne Emile
EE
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D047468:Immunoprecipitation; D008297:Male; D008870:Microtubules / Q000378:metabolism*; D016716:PC12 Cells; D010641:Phenotype; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D014404:Tubulin; D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4