Your browser doesn't support javascript.
loading
FKBP51-Hsp90 Interaction-Deficient Mice Exhibit Altered Endocrine Stress Response and Sex Differences Under High-Fat Diet.
Wang, Lisha; Wojcieszak, Jakub; Kumar, Rajnish; Zhao, Zhe; Sun, Xuelian; Xie, Shaoxun; Winblad, Bengt; Pavlov, Pavel F.
Afiliação
  • Wang L; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164, Solna, Sweden.
  • Wojcieszak J; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164, Solna, Sweden.
  • Kumar R; Department of Pharmacodynamics, Medical University of Lodz, 90151, Lodz, Poland.
  • Zhao Z; Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), 221005, Varanasi, India.
  • Sun X; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164, Solna, Sweden.
  • Xie S; Department of Toxicology, School of Public Health, Peking University, 100191, Beijing, China.
  • Winblad B; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164, Solna, Sweden.
  • Pavlov PF; National Clinical Research Center for Geriatrics and Department of Gerontology and Geriatrics, West China Hospital, Sichuan University, 610041, Chengdu, China.
Mol Neurobiol ; 61(3): 1479-1494, 2024 Mar.
Article em En | MEDLINE | ID: mdl-37726498
ABSTRACT
FK506-binding protein 51 kDa (FKBP51), encoded by Fkbp5 gene, gained considerable attention as an important regulator of several aspects of human biology including stress response, metabolic dysfunction, inflammation, and age-dependent neurodegeneration. Its catalytic peptidyl-prolyl isomerase (PPIase) activity is mediated by the N-terminal FK506-binding (FK1) domain, whereas the C-terminal tetratricopeptide motif (TPR) domain is responsible for FKBP51 interaction with molecular chaperone heat shock protein 90 (Hsp90). To understand FKBP51-related biology, several mouse models have been created. These include Fkbp5 complete and conditional knockouts, overexpression, and humanized models. To dissect the role of FKBP51-Hsp90 interaction in FKBP51 biology, we have created an interaction-deficient mouse (Fkbp5TPRmut) by introducing two-point mutations in the TPR domain of FKBP51. FKBP51-Hsp90 interaction-deficient mice are viable, fertile and show Mendelian inheritance. Intracellular association of FKBP51 with Hsp90 is significantly reduced in homozygous mutants compared to wild-type animals. No behavioral differences between genotypes were seen at 2 months of age, however, sex-dependent differences were detected in Y-maze and fear conditioning tests at the age of 12 months. Moreover, we have found a significant reduction in plasma levels of corticosterone and adrenocorticotropic hormone in Fkbp5TPRmut mice after acute stress. In contrast to Fkbp5 knockout mice, females of Fkbp5TPRmut showed increased body weight gain under high-fat diet treatment. Our data confirm the importance of FKBP51-Hsp90 interactions for stress-related endocrine signaling. Also, Fkbp5TPRmut mice can serve as a useful in vivo tool to discriminate between Hsp90-dependent and independent functions of FKBP51.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caracteres Sexuais / Dieta Hiperlipídica Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caracteres Sexuais / Dieta Hiperlipídica Idioma: En Ano de publicação: 2024 Tipo de documento: Article