Similar Transcriptomic Alterations in Cx43 Knockdown and Knockout Astrocytes

Iacobaş, Dumitru A.; Iacobaş, Sanda; Urban-Maldonado, Márcia; Scemes, Eliana; Spray, David C.

doi:10.1080/15419060802014222

Cited by 49 publications

(45 citation statements)

References 34 publications

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“…Cx43 may form complexes with membrane receptors, cell signaling molecules, scaffolding proteins, cytoskeleton components, and other proteins independently of Cx43 hemichannel activity [134][135][136][137][138]. Deletion of genes encoding Cx32, Cx36, or Cx43 affected the transcription of unrelated genes [139,140]. Nevertheless, physiological, pharmacological, and genetic evidence support the hypothesis that connexin hemichannels contribute to ATP release in a variety of cell types.…”

Section: Connexinsmentioning

confidence: 99%

Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

250

225

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Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

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Section: Connexinsmentioning

confidence: 99%

Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

250

225

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“…An indirect confirmation of the "see-saw" model of the transcriptomic recovery came recently when two promyelinating treatments were reported to increase the level of the gap junction protein Cx43 (Roscoe et al 2007), whereas we have shown previously a significant downregulation of Cx43 in AT-EAE mouse spinal cord, an animal model of the human multiple sclerosis (Brand-Schieber et al 2005;Iacobas et al 2008b). In principle, the "seesaw" model can be considered as confirmed by the rescue obtained through overexpressing a positive partner or underexpressing a negative partner of the gene whose deletion caused the disease.…”

Section: The Perspective Of the "Transcriptomic See-saws"mentioning

confidence: 99%

Integrated transcriptomic response to cardiac chronic hypoxia: translation regulators and response to stress in cell survival

Iacobaş

Fan

Iacobaş

et al. 2008

Funct Integr Genomics

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Complementary deoxyribonucleic acid microarray data from 36 mice subjected for 1, 2, or 4 weeks of their early life to normal atmospheric conditions (normoxia) or chronic intermittent (CIH) or constant (CCH) hypoxia were analyzed to extract organizational principles of the developing heart transcriptome and determine the integrated response to oxygen deprivation. Although both CCH and CIH regulated numerous genes involved in a wide diversity of processes, the changes in maturational profile, expression stability, and coordination were vastly different between the two treatments, indicating the activation of distinct regulatory mechanisms of gene transcription. The analysis focused on the main regulators of translation and response to stress because of their role in the cardiac hypertrophy and cell survival in hypoxia. On average, the expression of each heart gene was tied to the expression of about 20% of other genes in normoxia but to only 8% in CCH and 9% in CIH, indicating a strong decoupling effect of hypoxia. In contrast to the general tendency, the interlinkages among components of the translational machinery and response to stress increased significantly in CIH and much more in CCH, suggesting a coordinated response to the hypoxic stress. Moreover, the transcriptomic networks were profoundly and differently remodeled by CCH and CIH.

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“…(1) full-length Cx43 driven by the cytomegalovirus (CMV) promoter (CMV-Cx43) (Fu et al, 2004); (2) C-terminally truncated Cx43 tagged with GFP [Cx43⌬244 -382GFP (Cx43t-GFP)] (Bates et al, 2007); (3) U6 -Cx43siRNA [sequence, CAATTCCTCCTGCCGCAAT (Iacobas et al, 2008); gift from Dr. Eliana Scemes, Albert Einstein College of Medicine, Bronx, NY]; and (4) U6-control-siRNA (sequence, CTC-CTTTTTT; gift from Dr. Timothy O'Connor, University of British Columbia, British Columbia, Canada). The introduction of DNA by in utero electroporation was conducted as described previously (Tabata and Nakajima, 2002;Barnabé-Heider et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Involvement of the Cytoplasmic C-Terminal Domain of Connexin43 in Neuronal Migration

Cina

Maass²,

Theis³

et al. 2009

J. Neurosci.

140

146

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During brain development, young neurons closely associate with radial glial while migrating from the ventricular zone (VZ) to the cortical plate (CP) of the neocortex. It has been shown previously that gap junctions are needed for this migration to occur properly, but the precise mechanism responsible is still in question. Here, we used Cre recombinase, driven by the nestin promoter, to conditionally knock-out a floxed coding DNA of the connexin43 (Cx43) gene in mice. Radial glia in the VZ normally express connexin43. They undergo divisions that produce neurons and astrocytes and serve as migratory guides for the daughter cells that they produce. Based on histological analysis, we suggest that removing Cx43 from radial glia alters the normal lamination of the mouse neocortex. To monitor newborn neurons during development, we introduced a plasmid containing green fluorescent protein driven by a neuronal (T␣1 tubulin) promoter into the embryonic neocortex using in utero electroporation. The transfected migrating neurons remain in the VZ/intermediate zone (IZ) of the Cx43 conditional knock-out (Cx43cKO) animals, whereas in Cx43fl/fl mice, neurons migrate through the IZ into the CP, indicating that deletion of Cx43 from nestin-positive cells disrupts neuronal migration. We were able to rescue migration of Cx43cKO neurons by electroporating a cytomegalovirus-Cx43 expression plasmid into the embryonic cortex. In contrast, a C-terminal truncated form of Cx43 failed to rescue neuronal migration. In addition, Cx43K258stop mice, in which Cx43 lacks the last 125 amino acid residues of the cytoplasmic C-terminal domain, gave results similar to those seen with the Cx43cKO mice. This study illustrates that deletion of the C-terminal domain of Cx43 alters neuronal migration in the neocortex.

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Similar Transcriptomic Alterations in Cx43 Knockdown and Knockout Astrocytes

Cited by 49 publications

References 34 publications

Vesicular and conductive mechanisms of nucleotide release

Vesicular and conductive mechanisms of nucleotide release

Integrated transcriptomic response to cardiac chronic hypoxia: translation regulators and response to stress in cell survival

Involvement of the Cytoplasmic C-Terminal Domain of Connexin43 in Neuronal Migration

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