Binding of hsp90-Associated Immunophilins to Cytoplasmic Dynein: Direct Binding and in Vivo Evidence that the Peptidylprolyl Isomerase Domain Is a Dynein Interaction Domain

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• 作者：Mario D. Galigniana ; Jennifer M. Harrell ; Patrick J. M. Murphy ; Michael Chinkers ; Christine Radanyi ; Jack-Michel Renoir ; Mingjie Zhang ; and William B. Pratt
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：November 19, 2002
• 年：2002
• 卷：41
• 期：46
• 页码：13602 - 13610
• 全文大小：1303K
• 年卷期：v.41,no.46(November 19, 2002)
• ISSN：1520-4995

文摘

FKBP52 is a steroid receptor-associated immunophilin that binds via a tetratricopeptide repeat(TPR) domain to hsp90. FKBP52 has also been shown to interact either directly or indirectly via itspeptidylprolyl isomerase (PPIase) domain with cytoplasmic dynein, a motor protein involved in retrogradetransport of vesicles toward the nucleus. The functional role for the PPIase domain in receptor movementwas demonstrated by showing that expression of the PPIase domain fragment of FKBP52 in 3T3 cellsinhibits dexamethasone-dependent nuclear translocation of a green fluorescent protein-glucocorticoidreceptor chimera. Here, we show that cytoplasmic dynein is co-immunoadsorbed with two other TPRdomain proteins that bind hsp90 (the cyclophilin CyP-40 and the protein phosphatase PP5). Both proteinspossess PPIase homology domains, and co-immunoadsorption of cytoplasmic dynein with each is blockedby the PPIase domain fragment of FKBP52. Using purified proteins, we show that FKBP52, PP5, and thePPIase domain fragment bind directly to the intermediate chain of cytoplasmic dynein. PP5 colocalizeswith both cytoplasmic dynein and microtubules, and expression of the PPIase domain fragment of FKBP52in 3T3 cells disrupts its cytoskeletal localization. We conclude that the PPIase domains of the hsp90-binding immunophilins interact directly with cytoplasmic dynein and that this interaction with the motorprotein is responsible for the microtubular localization of PP5 in vivo.