AMOT130 linking F-actin to YAP is involved in intervertebral disc degeneration.

OBJECTIVES:Dysregulation of YAP by the Hippo signalling is associated with intervertebral disc degeneration (IDD). However, the relationship between the F-actin and Hippo pathway in IDD, and their effects on YAP remain poorly understood. METHODS:The characteristics of Hippo pathway and F-actin the in the NP (nucleus pulposus) and annulus fibrosus of immature, mature, ageing and disc degeneration model rats were observed by immunofluorescence, western blot and qPCR. Nucleus pulposus cells (NPCs) were transfected with lentivirus Sh-LATS A, Sh-LATS B and harvested for SA-β-gal staining, qPCR, western blotting and immunofluorescence staining to investigate the mechanism of Hippo pathway and F-actin interact in NPCs. RESULTS:We observed moderate decreases in F-actin and YAP expression with age in healthy intervertebral discs (IVDs). F-actin stress fibres distributed throughout the cytoplasm disappeared following treatment with latrunculin B (Lat B), resulting in a punctate distribution. Depletion of large tumour suppressor homologues 1/2 (LATS1/2) did not decrease the rate of cellular senescence, and YAP remained in the cytoplasm following Lat B treatment. Furthermore, angiomotin 130 (AMOT130) was associated with F-actin through a conserved actin-binding domain to retain YAP in the cytoplasm. CONCLUSIONS:This study showed that a mechanism by which Hippo pathway and F-actin synergize to modulate YAP activation and localization in the context of IDD and help to control NPCs proliferation. © 2018 John Wiley & Sons Ltd.

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