Connexin23 deletion does not affect lens transparency

Berthoud, Viviana M.; Minogue, Peter J.; Snabb, Joseph I.; Dzhashiashvili, Yulia; Novak, L.A.; Zoltoski, Rebecca K.; Popko, Brian; Beyer, Eric C.

doi:10.1016/j.exer.2016.03.025

Cited by 5 publications

(3 citation statements)

References 30 publications

(42 reference statements)

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“…Transcripts for a fourth lens connexin, Cx23, have been identified in zebrafish embryo and mouse lenses [ 10 – 12 ]. In mouse lens fiber cells, the abundance of Cx23 protein is similar to Cx46, but lower than Cx50 [ 13 ]; however, Cx23 knockout mice have transparent lenses [ 14 ]. In the human lens, expression of Cx23 has not been reported, and it has been suggested that the Cx23 gene is inactivated in primates [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Focus on lens connexins

Berthoud

Ngezahayo

2017

BMC Cell Biol

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The lens is an avascular organ composed of an anterior epithelial cell layer and fiber cells that form the bulk of the organ. The lens expresses connexin43 (Cx43), connexin46 (Cx46) and connexin50 (Cx50). Epithelial Cx50 has critical roles in cell proliferation and differentiation, likely involving growth factor-dependent signaling pathways. Both Cx46 and Cx50 are crucial for lens transparency; mutations in their genes have been linked to congenital and age-related cataracts. Congenital cataract-associated connexin mutants can affect protein trafficking, stability and/or function, and the functional effects may differ between gap junction channels and hemichannels. Dominantly inherited cataracts may result from effects of the connexin mutant on its wild type isotype, the other co-expressed wild type connexin and/or its interaction with other cellular components.

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Section: Introductionmentioning

confidence: 99%

Focus on lens connexins

Berthoud

Ngezahayo

2017

BMC Cell Biol

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“…Collectively, these findings place Cx31.1 into an unusual category of having little or no ability of being able to form functional gap junction channels when expressed in the absence of other connexins. Although Cx23 is another connexin that fails to form gap junction channels, Cx23 transcripts have not been discovered in primate cDNA libraries suggesting the GJIC incompetency of Cx23 is likely due to gene inactivation, unlike Cx31.1, which has been identified at the protein and transcript level in several human cell types ( Sonntag et al, 2009 ; Berthoud et al, 2016 ). Thus, Cx31.1 is in a unique category of connexin isoforms exhibiting little capacity to form gap junction channels on its own in tissue-relevant keratinocytes, even though it is present at the mRNA and protein levels in keratinocytes and other cell types ( Goliger and Paul, 1994 ; Di et al, 2001 ; Kibschull et al, 2004 ; Shurman et al, 2005 ; Wiszniewski et al, 2007 ; Dere et al, 2008 ; Wang et al, 2009 ; Serre-Beinier et al, 2009 ; Zhang et al, 2012 ; Kibschull et al, 2014 ; Zhai et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Cx31.1 can selectively intermix with co-expressed connexins to facilitate its assembly into gap junctions

Leighton,

Wong,

Lucaciu

et al. 2024

Journal of Cell Science

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Connexins are channel forming proteins that function to facilitate gap junctional intercellular communication. Here we use dual cell voltage clamp and dye transfer studies to corroborate past findings that Cx31.1 is defective in gap junction channel formation; illustrating that Cx31.1 alone does not form functional gap junction channels in connexin-deficient cells. Rather Cx31.1 transiently localizes to the secretory pathway with a subpopulation reaching the cell surface which is rarely seen in puncta reminiscent of gap junctions. Intracellular retained Cx31.1 was subject to degradation as Cx31.1 accumulated in the presence of proteasomal inhibition, had a faster turnover when Cx43 was present, and ultimately reached lysosomes. While intracellularly retained Cx31.1 was found to interact with Cx43, this interaction did not rescue its delivery to the cell surface. Conversely, the co-expression of Cx31 dramatically rescued the assembly of Cx31.1 into gap junctions where gap junction-mediated dye transfer was enhanced. Collectively, our results indicate that the localization and functional status of Cx31.1 is altered through selective interplay with co-expressed connexins, perhaps suggesting Cx31.1 is a key regulator of intercellular signalling in keratinocytes.

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“…Cx46 forms gap junction channels between fiber cells in bovine ( Paul et al, 1991 ; Tenbroek et al, 1992 ), chicken ( Biswas et al, 2010 ), mouse ( Gong et al, 1998 ; Berthoud et al, 2016 ), and monkey ( Lo et al, 1996 ) lenses. The current evidence based on the association of cataract development with Cx46 mutations strongly supports the notion that Cx46 also forms gap junction channels in human fiber cells ( Jiang, 2010 ; Retamal et al, 2015 ; Berthoud and Ngezahayo, 2017 ; Berthoud et al, 2020 ).…”

Section: Connexins In the Lensmentioning

confidence: 99%

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

Retamal

Altenberg

2022

Front. Physiol.

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Connexins are a family of proteins that can form two distinct types of channels: hemichannels and gap junction channels. Hemichannels are composed of six connexin subunits and when open allow for exchanges between the cytoplasm and the extracellular milieu. Gap junction channels are formed by head-to-head docking of two hemichannels in series, each one from one of two adjacent cells. These channels allow for exchanges between the cytoplasms of contacting cells. The lens is a transparent structure located in the eye that focuses light on the retina. The transparency of the lens depends on its lack of blood irrigation and the absence of organelles in its cells. To survive such complex metabolic scenario, lens cells express Cx43, Cx46 and Cx50, three connexins isoforms that form hemichannels and gap junction channels that allow for metabolic cooperation between lens cells. This review focuses on the roles of Cx46 hemichannels and gap junction channels in the lens under physiological conditions and in the formation of cataracts, with emphasis on the modulation by posttranslational modifications.

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Connexin23 deletion does not affect lens transparency

Cited by 5 publications

References 30 publications

Focus on lens connexins

Focus on lens connexins

Cx31.1 can selectively intermix with co-expressed connexins to facilitate its assembly into gap junctions

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

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