Intracellular signaling in osteocytes activated by mechanical loading is important for bone formation and remodeling. These signaling events are mediated by small modulators released from C×43 hemichannels (HC). We have recently shown that integrin α5 senses the mechanical stimulation and induces the opening of C×43 HC; however, the underlying mechanism is unknown. Here, we show that both C×43 and integrin α5 interact with 14-3-3θ, and this interaction is required for the opening of C×43 HC upon mechanical stress. The absence of 14-3-3θ prevented the interaction between C×43 and integrin α5, and blocked HC opening. Furthermore, it decreased the transport of C×43 and integrin α5 from the Golgi apparatus to the plasma membrane. Mechanical loading promoted the movement of C×43 to the surface which was associated not only with an increase in 14-3-3θ levels but also its interaction with C×43 and integrin α5. This stimulatory effect on forward transport by mechanical loading was attenuated in the absence of 14-3-3θ and the majority of the C×43 accumulated in the Golgi. Disruption of the Golgi by brefeldin A reduced the association of C×43 and integrin α5 with 14-3-3θ, further suggesting that the interaction is likely to occur in the Golgi. Together, these results define a previously unidentified, scaffolding role of 14-3-3h in assisting the delivery of C×43 and integrin α5 to the plasma membrane for the formation of mechanosensitive HC in osteocytes.
ASJC Scopus subject areas
- Cell Biology