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. 2022 Mar 9;8(10):eabi4797. doi: 10.1126/sciadv.abi4797

Fig. 3. FKBP51 associates with AMPK, TSC2, and WIPI3 and WIPI4 to regulate autophagy and mTOR signaling.

Fig. 3.

(A) Published protein-protein interactions of FKBP51. (B) FKBP51 associates with WIPI3 and WIPI4, but not with WIPI1 and WIPI2. WCE, whole-cell extract; IP, immunoprecipitation. (C) Interaction of FKBP51 with AMPK subunits. (D) Interaction of FKBP51 with LKB1 and AMPKα in WIPI4 KD cells. (E) Interaction of WIPI4 with AMPKα in FKBP51-lacking cells. (F) FKBP51 interacts with TSC2 in dependency of WIPI3. (G) WIPI3 interacts with TSC2 and TSC1 in the presence or absence of FKBP51. (H) Identified associations of FKBP51 in the regulation of autophagy and mTOR signaling and the proposed model of interaction. FKBP51 recruits LKB1 to the AMPK-WIPI4 complex and thereby facilitates AMPK activation. Furthermore, FKBP51 scaffolds TSC2-WIPI3 binding to alter mTOR signaling. AB, antibody.