Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels

Batra, Nidhi; Burra, Sirisha; Siller-Jackson, Arlene J.; Gu, Sumin; Xia, Xuan; Weber, Gregory F.; DeSimone, Douglas W.; Bonewald, Lynda F.; Lafer, Eileen M.; Sprague, Eugene A.; Schwartz, Martin A.; Jiang, Jean X.

doi:10.1073/pnas.1115967109

Cited by 217 publications

(220 citation statements)

References 35 publications

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“…Moreover, they are triggered to open by some stimulation, such as inflammation, mechanical stress or ischemia (Batra et al, 2012;Johansen et al, 2011;Karpuk et al, 2011). In our study, however, we demonstrated for the first time that connexin-mediated hemichannels are responsible for glucose uptake in OPCs, implying a role for oligodendroglial connexin hemichannels under physiological conditions.…”

Section: Inhibition Of Hemichannel Activity Impacts Opc Proliferationmentioning

confidence: 61%

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Niu

et al. 2016

Journal of Cell Science

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Oligodendrocyte precursor cells (OPCs) undergo a series of energyconsuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca 2+ elevation in OPCs, indicating a Ca 2+ -dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energymetabolism-directed oligodendroglial-targeted therapies.

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Section: Inhibition Of Hemichannel Activity Impacts Opc Proliferationmentioning

confidence: 61%

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Niu

et al. 2016

Journal of Cell Science

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“…via conformational changes, which could be induced by mechanical stimuli (55)(56)(57). The conformational activation of integrin ␣5␤1 might also play a crucial role in the process of ESW-induced adhesion and migration of osteoblasts.…”

Section: Journal Of Biological Chemistry 26207mentioning

confidence: 99%

Optimal Intensity Shock Wave Promotes the Adhesion and Migration of Rat Osteoblasts via Integrin β1-mediated Expression of Phosphorylated Focal Adhesion Kinase

Chen

et al. 2012

Journal of Biological Chemistry

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Background:The effects of extracorporeal shock wave (ESW) on adhesion and migration of osteoblasts have not been reported until now. Results: Optimal intensity shock wave promotes osteoblast adhesion and migration. Conclusion: ESW promotes the adhesion and migration of osteoblasts via integrin ␤1-mediated expression of phosphorylated FAK.Significance: This provides a mechanistic basis for improving the effectiveness of ESW treatment in fracture healing and tissue engineering.

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“…We have previously shown that FFSS increases the assembly and cell surface expression of Cx43 HC (Siller-Jackson et al, 2008). We recently demonstrated that integrin a5 interacts with Cx43 in osteocytic cells and this interaction, in conjunction with the activation of integrin a5, is required for the opening of Cx43 HC in response to mechanical loading (Batra et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

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

Batra

Riquelme

Burra

et al. 2013

Journal of Cell Science

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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 Cx43 hemichannels (HC). We have recently shown that integrin a5 senses the mechanical stimulation and induces the opening of Cx43 HC; however, the underlying mechanism is unknown. Here, we show that both Cx43 and integrin a5 interact with 14-3-3h, and this interaction is required for the opening of Cx43 HC upon mechanical stress. The absence of 14-3-3h prevented the interaction between Cx43 and integrin a5, and blocked HC opening. Furthermore, it decreased the transport of Cx43 and integrin a5 from the Golgi apparatus to the plasma membrane. Mechanical loading promoted the movement of Cx43 to the surface which was associated not only with an increase in 14-3-3h levels but also its interaction with Cx43 and integrin a5. This stimulatory effect on forward transport by mechanical loading was attenuated in the absence of 14-3-3h and the majority of the Cx43 accumulated in the Golgi. Disruption of the Golgi by brefeldin A reduced the association of Cx43 and integrin a5 with 14-3-3h, 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 Cx43 and integrin a5 to the plasma membrane for the formation of mechanosensitive HC in osteocytes.

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Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels

Cited by 217 publications

References 35 publications

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Optimal Intensity Shock Wave Promotes the Adhesion and Migration of Rat Osteoblasts via Integrin β1-mediated Expression of Phosphorylated Focal Adhesion Kinase

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

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