FKBP12 contributes to α-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome.

ABSTRACT: Calcineurin is an essential Ca²⁺-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa cis-trans proline isomerase FK506-binding protein (FKBP12). Whether calcineurin/FKBP12 represents a native physiologically relevant assembly that occurs in the absence of pharmacological perturbation has remained elusive. We leveraged α-syn as a model to interrogate whether FKBP12 plays a role in regulating calcineurin activity in the absence of Tacrolimus. We show that FKBP12 profoundly affects the calcineurin-dependent phosphoproteome, promoting the depho

SUBMITTER: Caraveo G 

PROVIDER: S-EPMC5748183 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature