Stimulation of Lens Cell Differentiation by Gap Junction Protein Connexin 45.6

Gu, Sumin; Yu, X. Sean; Yin, Xinye; Jiang, Jean X.

doi:10.1167/iovs.02-1045

Cited by 45 publications

(57 citation statements)

References 44 publications

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“…1A, lane 3) and the mutants Cx45.6(D47A) (lane 1) and P88S (lane 2). Similar to the expression pattern of wild-type Cx45.6 we reported previously (Gu et al, 2003) and Cx56 , high-resolution immunofluorescence confocal microscope experiments with antibodies against the FLAG epitope tag and against Cx45.6 revealed in primary cultured lens cells that the Cx45.6 mutants distributed primarily to the lentoid structures. The staining patterns with sharp outlines indicate a membrane localization for Cx45.6 and the corresponding mutants (Fig.…”

Section: Resultssupporting

confidence: 84%

“…2). As we reported previously, with retroviral infection, almost all cells express exogenous connexins (Jiang, 2001;Gu et al, 2003). In addition, CEF cells do not express native Cx45.6.…”

Section: Resultssupporting

confidence: 69%

“…We have previously shown that overexpression of wild-type Cx45.6 induces an ~100% increase in the amount of MIP(AQP0) over wild-type Cx45.6 (Gu et al, 2003). Compared with protein levels of vehicle and ␤-actin controls, western blots of membrane preparations with antibody against Cx45.6 and densitometric measurements revealed the increased expression of Cx45.6 and mutants in all connexinoverexpressing cultures (Fig.…”

Section: Resultsmentioning

confidence: 79%

“…Cx50 missense mutant P88S at the second transmembrane domain, associated with human autosomal dominant-negative cataracts, has been reported not only to fail to form functional gap junctions but also to act as a dominantnegative mutant that inhibits wild-type connexins from forming gap junctions (Shiels et al, 1998;Pal et al, 1999). We previously have shown that one of the lens connexins, Cx45.6, unlike the other two types of lens connexins, stimulates epithelial-fiber cell differentiation and expression of major differentiation markers (Gu et al, 2003). Moreover, this stimulatory effect appears to be independent of lens cell proliferation and intercellular coupling.…”

Section: Introductionmentioning

confidence: 98%

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Promotion of lens epithelial-fiber differentiation by the C-terminus of connexin 45.6 – a role independent of gap junction communication

Banks¹,

Yu²,

Shi³

et al. 2007

Journal of Cell Science

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We previously reported that, among the three connexins expressed in chick lens, overexpression of connexin (Cx) 45.6, not Cx43 or Cx56, stimulates lens cell differentiation; however, the underlying mechanism responsible for this effect is unclear. Here, we took advantage of naturally occurring loss-of-gap-junction function mutations of Cx50 (ortholog of chick Cx45.6) and generated the corresponding site mutants in Cx45.6: Cx45.6(D47A) and Cx45.6(P88S). In contrast to wild-type Cx45.6, the mutants failed to form functional gap junctions, and Cx45.6(P88S) and, to a lesser degree, Cx45.6(D47A) functioned in a dominant-negative manner. Interestingly, overexpression of both mutants incapable of forming gap junctions significantly increased epithelial-fiber differentiation to a level comparable to that of wild-type Cx45.6. To map the functional domain of Cx45.6, we generated a C-terminus chimera as well as deletion mutants. Overexpression of Cx56*45.6C, the mutant in which the C-terminus of Cx56 was replaced with that of Cx45.6, had a stimulatory effect on lens cell differentiation similar to that of Cx45.6. However, cells overexpressing Cx45.6*56C, the mutant in which C-terminus of Cx45.6 was replaced with that of Cx56, and Cx45.6(-C), in which the C-terminus was deleted, failed to promote differentiation. Taken together, we conclude that the expression of Cx45.6, but not Cx45.6-dependent gap junction channels, is involved in lens epithelial-fiber cell differentiation, and the C-terminal domain of Cx45.6 plays a predominant role in mediating this process.Supplementary material available online at

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Section: Resultssupporting

confidence: 84%

“…2). As we reported previously, with retroviral infection, almost all cells express exogenous connexins (Jiang, 2001;Gu et al, 2003). In addition, CEF cells do not express native Cx45.6.…”

Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Promotion of lens epithelial-fiber differentiation by the C-terminus of connexin 45.6 – a role independent of gap junction communication

Banks¹,

Yu²,

Shi³

et al. 2007

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

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“…Such morphogenetic control could be exerted by GJC-mediated changes in differentiation (Zhang et al, 2002;Araya et al, 2003Araya et al, , 2005Gu et al, 2003;Hirschi et al, 2003), proliferation (Paraguassu-Braga et al, 2003;Pearson et al, 2005), or cell migration (Minkoff et al, 1997;Huang et al, 1998;Lecanda et al, 2000;OviedoOrta et al, 2002;Kjaer et al, 2004). To integrate GJC-dependent signals into the systems that control complex morphology, it is necessary to understand the factors regulating spatial flows of signals through gap junctions.…”

Section: Behavior Is Dependent Upon Gap Junction (Gj) -Mediated Signalsmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

et al. 2018

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Stem cells hold great promise for widespread biomedical applications, for which stem cell fate needs to be well tailored. Besides biochemical cues, accumulating evidence has demonstrated that spatiotemporal biophysical cues (especially mechanical cues) imposed by cell microenvironments also critically impact on the stem cell fate. As such, various biomaterials, especially hydrogels due to their tunable physicochemical properties and advanced fabrication approaches, are developed to spatiotemporally manipulate biophysical cues in vitro so as to recapitulate the 3D mechanical microenvironment where stem cells reside in vivo. Here, the main mechanical cues that stem cells experience in their native microenvironment are summarized. Then, recent advances in the design of hydrogel materials with spatiotemporally tunable mechanical properties for engineering 3D the spatiotemporal mechanical microenvironment of stem cells are highlighted. These in vitro engineered spatiotemporal mechanical microenvironments are crucial for guiding stem cell fate and their potential biomedical applications are subsequently discussed. Finally, the challenges and future perspectives are presented.

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Stimulation of Lens Cell Differentiation by Gap Junction Protein Connexin 45.6

Cited by 45 publications

References 44 publications

Promotion of lens epithelial-fiber differentiation by the C-terminus of connexin 45.6 – a role independent of gap junction communication

Promotion of lens epithelial-fiber differentiation by the C-terminus of connexin 45.6 – a role independent of gap junction communication

Mathematical model of morphogen electrophoresis through gap junctions

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel‐Based Platform for Guiding Stem Cell Fate

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