Focus on lens connexins

Berthoud, Viviana M.; Ngezahayo, Anaclet

doi:10.1186/s12860-016-0116-6

Cited by 59 publications

(56 citation statements)

References 105 publications

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“…The lens is an avascular and transparent organ, whose cells are coupled by an extensive network of gap junctions that facilitates the exchange of ions and metabolites throughout the organ [142,143]. The mature lens is composed of fiber cells covered with a single layer of epithelial cells on the anterior hemisphere.…”

Section: Role Of Connexin Ubiquitination In the Regulation Of Gap Junmentioning

confidence: 99%

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Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Totland

Rasmussen

Knudsen

et al. 2019

Cell. Mol. Life Sci.

110

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Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of connexins, cells can rapidly alter the number of gap junction channels at the plasma membrane in response to extracellular or intracellular cues. Increasing evidence suggests that ubiquitination has important roles in the regulation of endoplasmic reticulum-associated degradation of connexins as well as in the modulation of gap junction endocytosis and post-endocytic sorting of connexins to lysosomes. In recent years, researchers have also started to provide insights into the physiological roles of connexin ubiquitination in specific tissue types. This review provides an overview of the advances made in understanding the roles of connexin ubiquitination in the regulation of gap junction intercellular communication and discusses the emerging physiological and pathophysiological implications of these processes.

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Section: Role Of Connexin Ubiquitination In the Regulation Of Gap Junmentioning

confidence: 99%

“…As new fiber cells arise, older cells are pushed toward the center and become mature lens fibers. The differentiation of epithelial cells into fiber cells involves cell elongation and loss of nuclei and organelles [142,143].…”

Section: Role Of Connexin Ubiquitination In the Regulation Of Gap Junmentioning

confidence: 99%

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Totland

Rasmussen

Knudsen

et al. 2019

Cell. Mol. Life Sci.

110

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“…Cx43 deubiquitylation may rescue the protein from lysosomal degradation, allowing its recycling back to the plasma membrane. also participates in slower physiological processes, such as cell growth and development (Belousov et al, 2017;Berthoud and Ngezahayo, 2017;Jagger and Forge, 2015;Lilly et al, 2016;Meens et al, 2015;Merrifield and Laird, 2016;Wei et al, 2004). For instance, Cx43-mediated intercellular communication has been described in immune-mediated processes, where gap junctions participate in the immunological synapse and promote the transfer of viral-and tumour-derived peptides and miRNA, allowing further stimulation and modulation of immune responses (Aucher et al, 2013;Bermudez-Fajardo et al, 2007;Mendoza-Naranjo et al, 2007;Neijssen et al, 2005).…”

Section: Cx43mentioning

confidence: 99%

Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes

Ribeiro-Rodrigues

Martins‐Marques

Morel

et al. 2017

Journal of Cell Science

139

159

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Communication is important to ensure the correct and efficient flow of information, which is required to sustain active social networks. A fine-tuned communication between cells is vital to maintain the homeostasis and function of multicellular or unicellular organisms in a community environment. Although there are different levels of complexity, intercellular communication, in prokaryotes to mammalians, can occur through secreted molecules (either soluble or encapsulated in vesicles), tubular structures connecting close cells or intercellular channels that link the cytoplasm of adjacent cells. In mammals, these different types of communication serve different purposes, may involve distinct factors and are mediated by extracellular vesicles, tunnelling nanotubes or gap junctions. Recent studies have shown that connexin 43 (Cx43, also known as GJA1), a transmembrane protein initially described as a gap junction protein, participates in all these forms of communication; this emphasizes the concept of adopting strategies to maximize the potential of available resources by reutilizing the same factor in different scenarios. In this Review, we provide an overview of the most recent advances regarding the role of Cx43 in intercellular communication mediated by extracellular vesicles, tunnelling nanotubes and gap junctions.

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“…Many mutations in their genes have been linked to congenital cataracts (summarized in https://cat-map.wustl.edu/; 37; reviewed in Ref. 4). To elucidate the mechanisms by which connexin mutants cause cataracts, we generated knock-in mice expressing a mutant Cx46, Cx46fs380.…”

Section: Introductionmentioning

confidence: 99%

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

Gao

Minogue

Beyer

et al. 2018

American Journal of Physiology-Cell Physiology

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The lens is an avascular organ whose function and survival depend on an internal circulation system. Cx46fs380 mice model a human autosomal dominant cataract caused by a mutant lens connexin. In these mice, fiber cell connexin levels and gap junction coupling are severely decreased. The present studies were conducted to examine components of the lens circulation system that might be altered and contribute to the pathogenesis of cataracts. Lenses from wild-type mice and Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age. Cx46fs380-expressing lens fiber cells were depolarized. Cx46fs380 lenses had increased intracellular hydrostatic pressure and concentrations of Na and Ca. The activity of epithelial Na-K-ATPase was decreased in Cx46fs380 lenses. All of these changes were more severe in homozygous than in heterozygous Cx46fs380 lenses. Cx46fs380 cataracts were stained by Alizarin red, a dye used to detect insoluble Ca. These data suggest that the lens internal circulation was disrupted by expression of Cx46fs380, leading to several consequences including accumulation of Ca to levels so high that precipitates formed. Similar Ca-containing precipitates may contribute to cataract formation due to other genetic or acquired etiologies.

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Focus on lens connexins

Cited by 59 publications

References 105 publications

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes

Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice

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