Discrete cortical control during quiet stance revealed by desynchronization and rebound of beta oscillations.

Postural sway during quiet stance often exhibits a repetition of micro-fall and the subsequent micro-recovery. The classical view -that the quiet bipedal stance is stabilized by the ankle joint stiffness- has been challenged by paradoxical non-spring-like behaviors of calf muscles: gastrocnemius muscles are shortened and then lengthened, respectively, during the micro-fall and the micro-recovery. Here, we examined EEG based brain activity during quiet stance, and identified desynchronization and synchronization of beta oscillations that were associated, respectively, with the micro-fall and the micro-recovery. Based on a widely accepted scenario for beta-band desynchronization during movement and post-movement rebound in the control of discrete voluntary movement, our results reveal that the beta rebound can be considered as a manifestation of stop command to punctuate the motor control for every fall-recovery cycle. Namely, cortical interventions to the automatic postural control are discrete, rather than continuous modulations. The finding is highly compatible with the intermittent control model, rather than the stiffness control model.

The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity.

YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP's functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP's co-activation of TEAD-mediated CTGF transcription.