Abstract
The FK506-binding protein 52 (FKBP52) belongs to a large family of ubiquitously expressed and highly conserved proteins (FKBPs) that share an FKBP domain and possess Peptidyl-Prolyl Isomerase (PPIase) activity. PPIase activity catalyzes the isomerization of Peptidyl-Prolyl bonds and therefore influences target protein folding and function. FKBP52 is particularly abundant in the nervous system and is partially associated with the microtubule network in different cell types suggesting its implication in microtubule function. Various studies have focused on FKBP52, highlighting its importance in several neuronal microtubule-dependent signaling pathways and its possible implication in neurodegenerative diseases such as tauopathies (i.e., Alzheimer disease) and alpha-synucleinopathies (i.e., Parkinson disease). This review summarizes our current understanding of FKBP52 actions in the microtubule environment, its implication in neuronal signaling and function, its interactions with other members of the FKBPs family and its involvement in neurodegenerative disease.
Highlights
Academic Editors: Lucio TremolizzoFK506-binding proteins (FKBPs) belong to a subclass of the highly conserved immunophilin family which comprises a number of multifunctional proteins originally defined by their capacity to bind the immunomodulator FK506
We showed that FK506-binding protein 52 (FKBP52) modulates autophagylysosomal pathway (ALP) function during Tau-induced proteotoxic stress by modulating perinuclear lysosomal positioning and clustering, an important lysosomal process involved in protein degradation during stress [61]
We proposed that FKBP52 might play a role in Tau degradation [12,139], and we showed that FKBP52 is present in the endolysosomal system of human brain neurons [61]
Summary
FK506-binding proteins (FKBPs) belong to a subclass of the highly conserved immunophilin family which comprises a number of multifunctional proteins originally defined by their capacity to bind the immunomodulator FK506. PPIase activity is known to be inhibited by immuno-suppressant molecules such as FK506 and Rapamycin via a gain of function mechanism mediating immune suppression [3–5]. This activity provides new perspectives to elaborate original therapeutic strategies targeting FKBPs and their ligands. FKBP52, one of the larger FKBPs localized both in the nucleus and the cytoplasm, is composed of four functional domains ([68]; Figure 1): two consecutive FK506-binding domains namely FK1 (residues 31–139) and FK2 (residues 149–267), a TetratricoPeptide. FKBP52 is the presence in the third domain of a TPR with a chaperone activity [71] which is a binding site for the molecular heat shock protein chaperone of 90kDa (Hsp90) [72]
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