Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Hu, Zhengping; Shi, Wen; Riquelme, Manuel A.; Shi, Qian; Biswas, Sondip K.; Lo, Woo-Kuen; White, Thomas W.; Gu, Sumin; Jiang, Jean X.

doi:10.1038/s41598-017-05647-9

Cited by 25 publications

(33 citation statements)

References 37 publications

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“…To elucidate the effect of oxidative stress on lens connexin hemichannel activity, we infected chick embryo fibroblast (CEF) cells with recombinant RCAS(A) retrovirus containing FLAG-tagged wild-type Cx50 and/ or Cx50 mutants (E48K, P88S and H156N), and treated the cells with H 2 O 2 . As we reported previously, we have not detected expression of other possible connexin subtypes or the activities of connexin channels in these cells (Banks et al, 2007;Hu et al, 2017). With retroviral infection, almost all CEF cells express exogenous connexins (Gu et al, 2003;Jiang, 2001).…”

Section: Connexin Hemichannels Open Upon H 2 O 2 Treatment But This Isupporting

confidence: 54%

Connexin hemichannels mediate glutathione transport and protect lens fiber cells from oxidative stress

Shi

Riquelme

et al. 2018

Journal of Cell Science

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Elevated oxidized stress contributes to lens cataracts, and gap junctions play important roles in maintaining lens transparency. As well as forming gap junctions, connexin (Cx) proteins also form hemichannels. Here, we report a new mechanism whereby hemichannels mediate transport of reductant glutathione into lens fiber cells and protect cells against oxidative stress. We found that Cx50 (also known as GJA8) hemichannels opened in response to HO in lens fiber cells but that transport through the channels was inhibited by two dominant-negative mutants in Cx50, Cx50P88S, which inhibits transport through both gap junctions and hemichannels, and Cx50H156N, which only inhibits transport through hemichannels and not gap junctions. Treatment with HO increased the number of fiber cells undergoing apoptosis, and this increase was augmented with dominant-negative mutants that disrupted both hemichannels formed from Cx46 (also known as GJA3) and Cx50, while Cx50E48K, which only impairs gap junctions, did not have such an effect. Moreover, hemichannels mediate uptake of glutathione, and this uptake protected lens fiber cells against oxidative stress, while hemichannels with impaired transport had less protective benefit from glutathione. Taken together, these results show that oxidative stress activates connexin hemichannels in the lens fiber cells and that hemichannels likely protect lens cell against oxidative damage through transporting extracellular reductants.

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Section: Connexin Hemichannels Open Upon H 2 O 2 Treatment But This Isupporting

confidence: 54%

Connexin hemichannels mediate glutathione transport and protect lens fiber cells from oxidative stress

Shi

Riquelme

et al. 2018

Journal of Cell Science

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“…Primary antibodies were detected with goat anti-rabbit IgG conjugated IRDye ® 800CW and goat anti-mouse IgG conjugated IRDye ® 680RD (1:15 000 dilution) using a Licor Odyssey Infrared Imager (Lincoln, NE, USA), as previously described. 74 The band intensity was quantified by densitometry using Image J software (NIH, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Connexin 43 hemichannels protect bone loss during estrogen deficiency

Hua

Tian

et al. 2019

Bone Res

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Estrogen deficiency in postmenopausal women is a major cause of bone loss, resulting in osteopenia, osteoporosis, and a high risk for bone fracture. Connexin 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability, bone formation, and remodeling. We showed here that estrogen deficiency reduced Cx43 expression and HC function. To determine if functional HCs protect osteocytes and bone loss during estrogen deficiency, we adopted an ovariectomy model in wild-type (WT) and two transgenic Cx43 mice: R76W (dominant-negative mutant inhibiting only gap junction channels) and Cx43 Δ130–136 (dominant-negative mutant compromising both gap junction channels and HCs). The bone mineral density (BMD), bone structure, and histomorphometric changes of cortical and trabecular bones after ovariectomy were investigated. Our results showed that the Δ130–136 transgenic cohort had greatly decreased vertebral trabecular bone mass compared to WT and R76W mice, associated with a significant increase in the number of apoptotic osteocyte and empty lacunae. Moreover, osteoclast surfaces in trabecular and cortical bones were increased after ovariectomy in the R76W and WT mice, respectively, but not in ∆130–136 mice. These data demonstrate that impairment of Cx43 HCs in osteocytes accelerates vertebral trabecular bone loss and increase in osteocyte apoptosis, and further suggest that Cx43 HCs in osteocytes protect trabecular bone against catabolic effects due to estrogen deficiency.

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“…Six connexins form a hemichannel, and two hemichannels from a pair of adjacent cells constitute a gap junction. Through their vital roles in cellular communication, connexins have been shown to be required for the differentiation and maturation of different organs, such as the heart, the eye, the skeleton and nervous tissue ( Moorer and Stains, 2017 ; Su et al, 2017 ; Hu et al, 2017 ). In the mammalian inner ear, connexin 26 (Cx26, encoded by the GJB2 gene) is the main connexin, and it assembles into gap junctions in all supporting cells and fibrocytes ( Ahmad et al, 2003 ; Kikuchi et al, 1995 ; Zhao and Yu, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Developmental abnormalities in supporting cell phalangeal processes and cytoskeleton in the Gjb2 knockdown mouse model

Chen

Xie

et al. 2018

Disease Models &Amp; Mechanisms

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Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common causes of hereditary hearing loss in humans, and previous studies showed postnatal development arrest of the organ of Corti in different Cx26-null mouse models. To explore the pathological changes and the mechanism behind the cochlear abnormalities in these mice further, we established transgenic mouse models by conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory brainstem responses were recorded and the morphological features in the organ of Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group displayed severe hearing loss at all frequencies, whereas mice in the P8 knockdown group showed nearly normal hearing. In the P8 knockdown group, the organ of Corti displayed normal architecture, and no ultrastructural changes were observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells did not develop into finger-like structures, and the formation of microtubules in the pillar cells was significantly reduced; moreover, the amount of acetylated α-tubulin was reduced in pillar cells. Our results indicate that Gjb2 participates in postnatal development of the cytoskeleton in pillar cells during structural maturation of the organ of Corti. In P0 knockdown mice, the reduction in microtubules in pillar cells might be responsible for the failure of the tunnel of Corti to open, and the malformed phalangeal processes might negatively affect the supporting framework of the organ of Corti, which would be a new mechanism of Gjb2-related hearing loss.

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Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Cited by 25 publications

References 37 publications

Connexin hemichannels mediate glutathione transport and protect lens fiber cells from oxidative stress

Connexin hemichannels mediate glutathione transport and protect lens fiber cells from oxidative stress

Connexin 43 hemichannels protect bone loss during estrogen deficiency

Developmental abnormalities in supporting cell phalangeal processes and cytoskeleton in the Gjb2 knockdown mouse model

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