The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation

被引:71
作者
Chambraud, Beatrice
Belabes, Hamida
Fontaine-Lenoir, Virginie
Fellous, Arlette
Baulieu, Etienne Emile
机构
[1] Univ Paris 11, INSERM, UMR 788, F-94276 Le Kremlin Bicetre, France
[2] Univ Bicetre, Ctr Hosp, MAPREG Co, Le Kremlin Bicetre, France
关键词
cytoskeleton; neurite differentiation; microtubule dynamics; FK506 binding protein;
D O I
10.1096/fj.06-7667com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2787 / 2797
页数:11
相关论文
共 57 条
[1]   Microtubules cut and run [J].
Baas, PW ;
Karabay, A ;
Qiang, L .
TRENDS IN CELL BIOLOGY, 2005, 15 (10) :518-524
[2]  
Bareille O, 1998, MEC IND MATER, V51, P52
[3]   AN IMMUNOPHILIN THAT BINDS M(R) 90,000 HEAT-SHOCK PROTEIN - MAIN STRUCTURAL FEATURES OF A MAMMALIAN P59 PROTEIN [J].
CALLEBAUT, I ;
RENOIR, JM ;
LEBEAU, MC ;
MASSOL, N ;
BURNY, A ;
BAULIEU, EE ;
MORNON, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (14) :6270-6274
[4]   Purification of brain tubulin through two cycles of polymerization-depolymerization in a high-molarity buffer [J].
Castoldi, M ;
Popova, AV .
PROTEIN EXPRESSION AND PURIFICATION, 2003, 32 (01) :83-88
[5]   OVEREXPRESSION OF P59-HBI (FKBP59), FULL-LENGTH AND DOMAINS, AND CHARACTERIZATION OF PPLASE ACTIVITY [J].
CHAMBRAUD, B ;
ROUVIEREFOURMY, N ;
RADANYI, C ;
HSIAO, K ;
PEATTIE, DA ;
LIVINGSTON, DJ ;
BAULIEU, EE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 196 (01) :160-166
[6]   Physiological role for the cochaperone FKBP52 in androgen receptor signaling [J].
Cheung-Flynn, J ;
Prapapanich, V ;
Cox, MB ;
Riggs, DL ;
Suarez-Quian, C ;
Smith, DF .
MOLECULAR ENDOCRINOLOGY, 2005, 19 (06) :1654-1666
[7]   C-terminal sequences outside the tetratricopeptide repeat domain of FKBP51 and FKBP52 cause differential binding to hsp90 [J].
Cheung-Flynn, J ;
Roberts, PJ ;
Riggs, DL ;
Smith, DF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :17388-17394
[8]  
Christner C., 2001, Mini-Reviews in Medicinal Chemistry, V1, P377, DOI 10.2174/1389557013406675
[9]   N-terminal stathmin-like peptides bind tubulin and impede microtubule assembly [J].
Clément, MJ ;
Jourdain, I ;
Lachkar, S ;
Savarin, P ;
Gigant, B ;
Knossow, M ;
Toma, F ;
Sobel, A ;
Curmi, PA .
BIOCHEMISTRY, 2005, 44 (44) :14616-14625
[10]   THE HSP56 IMMUNOPHILIN COMPONENT OF UNTRANSFORMED STEROID-RECEPTOR COMPLEXES IS LOCALIZED BOTH TO MICROTUBULES IN THE CYTOPLASM AND TO THE SAME NONRANDOM REGIONS WITHIN THE NUCLEUS AS THE STEROID-RECEPTOR [J].
CZAR, MJ ;
OWENSGRILLO, JK ;
YEM, AW ;
LEACH, KL ;
DEIBEL, MR ;
WELSH, MJ ;
PRATT, WB .
MOLECULAR ENDOCRINOLOGY, 1994, 8 (12) :1731-1741