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Barbara S. Stonestreet - One of the best experts on this subject based on the ideXlab platform.

  • ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses newborns and adults
    Brain Research, 2009
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 60% of gestation (3.0 ± 0.68, mean ± SD), than in those at 90% of gestation (1.7 ± 0.3), in newborn (1.8 ± 0.55), and adult sheep (0.84 ± 0.19), respectively. In contrast, Connexin-43 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 90% of gestation (0.44 ± 0.17), newborn (0.69 ± 0.12) and adult sheep (1.14 ± 0.13), than in those at 60% of gestation (0.05 ± 0.01). We conclude that (1) Connexin-32 and Connexin-43 protein are expressed early in fetal life and throughout development, (2) each Connexin displays a unique pattern of change with development, (3) Connexin-43 exhibited ontogenic increases in protein abundance, whereas, Connexin-32 exhibited reciprocal decreases in abundance late in fetal development, in newborn and adult sheep.

  • Ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses, newborns, and adults.
    Brain research, 2008
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P 

Grazyna B. Sadowska - One of the best experts on this subject based on the ideXlab platform.

  • ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses newborns and adults
    Brain Research, 2009
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 60% of gestation (3.0 ± 0.68, mean ± SD), than in those at 90% of gestation (1.7 ± 0.3), in newborn (1.8 ± 0.55), and adult sheep (0.84 ± 0.19), respectively. In contrast, Connexin-43 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 90% of gestation (0.44 ± 0.17), newborn (0.69 ± 0.12) and adult sheep (1.14 ± 0.13), than in those at 60% of gestation (0.05 ± 0.01). We conclude that (1) Connexin-32 and Connexin-43 protein are expressed early in fetal life and throughout development, (2) each Connexin displays a unique pattern of change with development, (3) Connexin-43 exhibited ontogenic increases in protein abundance, whereas, Connexin-32 exhibited reciprocal decreases in abundance late in fetal development, in newborn and adult sheep.

  • Ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses, newborns, and adults.
    Brain research, 2008
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P 

Thomas W. White - One of the best experts on this subject based on the ideXlab platform.

  • Connexins and Disease
    Cold Spring Harbor perspectives in biology, 2018
    Co-Authors: Mario Delmar, Dale W Laird, Christian C. Naus, Morten Schak Nielsen, Vytautas Verselis, Thomas W. White
    Abstract:

    Inherited or acquired alterations in the structure and function of Connexin proteins have long been associated with disease. In the present work, we review current knowledge on the role of Connexins in diseases associated with the heart, nervous system, cochlea, and skin, as well as cancer and pleiotropic syndromes such as oculodentodigital dysplasia (ODDD). Although incomplete by virtue of space and the extent of the topic, this review emphasizes the fact that Connexin function is not only associated with gap junction channel formation. As such, both canonical and noncanonical functions of Connexins are fundamental components in the pathophysiology of multiple Connexin related disorders, many of them highly debilitating and life threatening. Improved understanding of Connexin biology has the potential to advance our understanding of mechanisms, diagnosis, and treatment of disease.

  • Human diseases associated with Connexin mutations
    Biochimica et biophysica acta. Biomembranes, 2017
    Co-Authors: Miduturu Srinivas, Vytas K. Verselis, Thomas W. White
    Abstract:

    Gap junctions and hemichannels comprised of Connexins impact many cellular processes. Significant advances in our understanding of the functional role of these channels have been made by the identification of a host of genetic diseases caused by Connexin mutations. Prominent features of Connexin disorders are the inability of other Connexins expressed in the same cell type to compensate for the mutated one, and the ability of Connexin mutants to dominantly influence the activity of other wild-type Connexins. Functional studies have begun to identify some of the underlying mechanisms whereby Connexin channel mutation contributes to the disease state. Detailed mechanistic understanding of these functional differences will help to facilitate new pathophysiology driven therapies for the diverse array of Connexin genetic disorders. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.

  • Connexin channels in congenital skin disorders.
    Seminars in cell & developmental biology, 2016
    Co-Authors: Evelyn Lilly, Caterina Sellitto, Leonard M. Milstone, Thomas W. White
    Abstract:

    Gap junctions and hemichannels comprised of Connexins influence epidermal proliferation and differentiation. Significant advances in our understanding of the functional role of Connexins in the skin have been made by studying the diseases caused by Connexin mutations. Eleven clinically defined cutaneous disorders with an overlapping spectrum of phenotypes are caused by mutations in five different Connexin genes, highlighting that disease presentation must be deciphered with an understanding of how Connexin functions are affected. Increasing evidence suggests that the skin diseases produced by Connexin mutations result from dominant gains of function. In palmoplantar keratoderma with deafness, the Connexin 26 mutations transdominantly alter the function of wild-type Connexin 43 and create leaky heteromeric hemichannels. In keratitis-ichthyosis-deafness syndrome, different Connexin 26 mutations can either form dominant hemichannels with altered calcium regulation or increased calcium permeability, leading to clinical subtypes of this syndrome. It is only with detailed understanding of these subtle functional differences that we can hope to create successful pathophysiology driven therapies for the Connexin skin disorders.

  • gap junctions basic structure and function
    Journal of Investigative Dermatology, 2007
    Co-Authors: Gulistan Mese, Gabriele Richard, Thomas W. White
    Abstract:

    Gap junctions allow the exchange of ions, second messengers, and small metabolites between adjacent cells and are formed by two unrelated protein families, the pannexins and Connexins. Mutations in Connexin genes cause a variety of genetic disorders, implicating a critical role in tissue homeostasis. Association of congenital skin disorders to mutations in different Connexins has underscored the importance of gap junctional communication in the skin and its appendages. Here, we discuss the basic structure of gap junction channels and the function of Connexin genes that have been associated with human disorders to explore the physiology of intercellular communication in skin.

  • cloning and functional expression of invertebrate Connexins from halocynthia pyriformis
    FEBS Letters, 2004
    Co-Authors: Thomas W. White, Jennifer Litteral, Huan Wang, Peter R Brink
    Abstract:

    Unlike many other ion channels, unrelated gene families encode gap junctions in different animal phyla. Connexin and pannexin genes are found in deuterostomes, while protostomal species use innexin genes. Connexins are often described as vertebrate genes, despite the existence of invertebrate deuterostomes. We have cloned Connexin sequences from an invertebrate chordate, Halocynthia pyriformis. Invertebrate Connexins shared 25–40% sequence identity with human Connexins, had extracellular domains containing six invariant cysteine residues, coding regions that were interrupted by introns, and formed functional channels in vitro. These data show that gap junction channels based on Connexins are present in animals that predate vertebrate evolution.

Luc Leybaert - One of the best experts on this subject based on the ideXlab platform.

  • Connexins: substrates and regulators of autophagy
    BMC Cell Biology, 2016
    Co-Authors: Jegan Iyyathurai, Luc Leybaert, Jean-paul Decuypere, Catheleyne D’hondt, Geert Bultynck
    Abstract:

    Connexins mediate intercellular communication by assembling into hexameric channel complexes that act as hemichannels and gap junction channels. Most Connexins are characterized by a very rapid turn-over in a variety of cell systems. The regulation of Connexin turn-over by phosphorylation and ubiquitination events has been well documented. Moreover, different pathways have been implicated in Connexin degradation, including proteasomal and lysosomal-based pathways. Only recently, autophagy emerged as an important Connexin-degradation pathway for different Connexin isoforms. As such, conditions well known to induce autophagy have an immediate impact on the Connexin-expression levels. This is not only limited to experimental conditions but also several pathophysiological conditions associated with autophagy (dys)function affect Connexin levels and their presence at the cell surface as gap junctions. Finally, Connexins are not only substrates of autophagy but also emerge as regulators of the autophagy process. In particular, several Connexin isoforms appear to recruit pre-autophagosomal autophagy-related proteins, including Atg16 and PI3K-complex components, to the plasma membrane, thereby limiting their availability and capacity for regulating autophagy.status: publishe

  • Connexins: substrates and regulators of autophagy
    BMC Cell Biology, 2016
    Co-Authors: Jegan Iyyathurai, Luc Leybaert, Jean-paul Decuypere, Catheleyne D’hondt, Geert Bultynck
    Abstract:

    Connexins mediate intercellular communication by assembling into hexameric channel complexes that act as hemichannels and gap junction channels. Most Connexins are characterized by a very rapid turn-over in a variety of cell systems. The regulation of Connexin turn-over by phosphorylation and ubiquitination events has been well documented. Moreover, different pathways have been implicated in Connexin degradation, including proteasomal and lysosomal-based pathways. Only recently, autophagy emerged as an important Connexin-degradation pathway for different Connexin isoforms. As such, conditions well known to induce autophagy have an immediate impact on the Connexin-expression levels. This is not only limited to experimental conditions but also several pathophysiological conditions associated with autophagy (dys)function affect Connexin levels and their presence at the cell surface as gap junctions. Finally, Connexins are not only substrates of autophagy but also emerge as regulators of the autophagy process. In particular, several Connexin isoforms appear to recruit pre-autophagosomal autophagy-related proteins, including Atg16 and PI3K-complex components, to the plasma membrane, thereby limiting their availability and capacity for regulating autophagy.

  • Connexin 43 is an emerging therapeutic target in ischemia reperfusion injury cardioprotection and neuroprotection
    Pharmacology & Therapeutics, 2015
    Co-Authors: Rainer Schulz, Philipp Maximilian Gorge, Aniko Gorbe, Peter Ferdinandy, Paul D Lampe, Luc Leybaert
    Abstract:

    Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six Connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, Connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally Connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the Connexins, namely Connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of Connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of Connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

Edward G. Stopa - One of the best experts on this subject based on the ideXlab platform.

  • ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses newborns and adults
    Brain Research, 2009
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 60% of gestation (3.0 ± 0.68, mean ± SD), than in those at 90% of gestation (1.7 ± 0.3), in newborn (1.8 ± 0.55), and adult sheep (0.84 ± 0.19), respectively. In contrast, Connexin-43 abundance was higher (P < 0.05) in cerebral cortices of fetuses at 90% of gestation (0.44 ± 0.17), newborn (0.69 ± 0.12) and adult sheep (1.14 ± 0.13), than in those at 60% of gestation (0.05 ± 0.01). We conclude that (1) Connexin-32 and Connexin-43 protein are expressed early in fetal life and throughout development, (2) each Connexin displays a unique pattern of change with development, (3) Connexin-43 exhibited ontogenic increases in protein abundance, whereas, Connexin-32 exhibited reciprocal decreases in abundance late in fetal development, in newborn and adult sheep.

  • Ontogeny of Connexin 32 and 43 expression in the cerebral cortices of ovine fetuses, newborns, and adults.
    Brain research, 2008
    Co-Authors: Grazyna B. Sadowska, Edward G. Stopa, Barbara S. Stonestreet
    Abstract:

    Gap junctions are specialized membrane structures that mediate intercellular communication and facilitate passage of ions and small molecules between adjacent cells. Connexins comprise a multigene family of transmembrane proteins that form gap junctions. Connexin-32 and Connexin-43 are among the most abundant Connexins in brain and are highly expressed during development. Connexin-32 is expressed primarily in oligodendrocytes and Connexin-43 in astrocytes in adult brain. However, both Connexins are expressed in neurons during development. We examined the effects of ontogeny on Connexin-32 and Connexin-43 protein abundance in cerebral cortices of sheep during development. Western immunoblot was used to measure Connexin-32 and Connexin-43 expression in cerebral cortices of fetuses at 60%, 80%, and 90% of gestation, in newborn lambs and adult sheep. Values were expressed as ratios to a single adult control cerebral cortical sample. Connexin-32 abundance was higher (P