14-3-3θ facilitates plasma membrane delivery and function of mechanosensitive connexin 43 hemichannels

Nidhi Batra, Manuel A. Riquelme, Sirisha Burra, Jean X. Jiang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalJournal of cell science
Volume127
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • 14-3-3
  • Connexion
  • Hemichannel

ASJC Scopus subject areas

  • Cell Biology

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