Gap junctions in inherited human disease

Zoidl, Georg; Dermietzel, Rolf

doi:10.1007/s00424-010-0789-1

Cited by 58 publications

(28 citation statements)

References 161 publications

(149 reference statements)

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“…Given the relatively low specificity of gap junctions that allows passage of a wide variety of molecules, it is not surprising that they are involved in a wide variety of physiological functions in different cell types. In many cases our knowledge stems from the effects of human mutations in connexin genes and the effects of targeted gene disruptions in mice (149,630,787). In general, the association of genetic and acquired disturbance of connexin function with human diseases have emphasized the importance of proper intercellular communication and shed new light on the physiological role of gap junctions for recent reviews see (351, 787).…”

Section: Physiological Function In Cell-to-cell Communicationmentioning

confidence: 99%

Gap Junctions

Nielsen,

Nygaard Axelsen,

Sorgen

et al. 2012

Comprehensive Physiology

373

365

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Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell‐cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981‐2035, 2012.

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Section: Physiological Function In Cell-to-cell Communicationmentioning

confidence: 99%

Gap Junctions

Nielsen,

Nygaard Axelsen,

Sorgen

et al. 2012

Comprehensive Physiology

373

365

View full text Add to dashboard Cite

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“…169 Beyond Laure Gilleron for critically reading the manuscript. the BTB could be further examinated after toxicant deposition to go further into the fine analysis of the role of one membranous protein vs. the others in spermatogenesis.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

et al. 2011

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“…(Reviewed by Rackauskas et al [1]. ) Mutations in at least 10 of these connexin genes cause human disease, [2] including three connexins with significant CNS manifestations; these are the focus of this review. Here we emphasize the clinical phenotypes and current understanding of the pathogenesis of these genetic diseases, which will require a brief overview of connexin expression within CNS glial cells, reviewed in more detail elsewhere.…”

Section: Introductionmentioning

confidence: 99%

Gap junctions in inherited human disorders of the central nervous system

Abrams

Scherer

2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

102

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CNS glia and neurons express connexins, the proteins that form gap junctions in vertebrates. We review the connexins expressed by oligodendrocytes and astrocytes, and discuss their proposed physiologic roles. Of the 21 members of the human connexin family, mutations in three are associated with significant central nervous system manifestations. For each, we review the phenotype and discuss possible mechanisms of disease. Mutations in GJB1, the gene for connexin 32 (Cx32) cause the second most common form of Charcot-Marie-Tooth disease (CMT1X). Though the only consistent phenotype in CMT1X patients is a peripheral demyelinating neuropathy, CNS signs and symptoms have been found in some patients with CMT1X. Recessive mutations in GJC2, the gene for Cx47, are one cause of Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by nystagmus within the first 6 months of life, cerebellar ataxia by 4 years, and spasticity by 6 years of age. MRI imaging shows abnormal myelination. A different recessive GJC2 mutation causes a form of hereditary spastic paraparesis, which is a milder phenotype than PMLD. Dominant mutations in GJA1, the gene for Cx43, cause oculodentodigital dysplasia (ODDD), a pleitropic disorder characterized by oculo-facial abnormalities including micropthalmia, microcornia and hypoplastic nares, syndactyly of the fourth to fifth fingers and dental abnormalities. Neurologic manifestations, including spasticity and gait difficulties, are often but not universally seen. Recessive GJA1 mutations cause Hallermann-Streiff syndrome, a disorder showing substantial overlap with ODDD.

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Gap junctions in inherited human disease

Cited by 58 publications

References 161 publications

Gap Junctions

Gap Junctions

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

Gap junctions in inherited human disorders of the central nervous system

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