Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration.
Int J Mol Sci
; 19(8)2018 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-30049932
Under pro-inflammatory conditions, astrocytes become reactive and acquire a migratory phenotype. Our results show that hemichannels formed by connexin 43 (Cx43) play an important role in Thy-1-induced astrocyte migration. The neuronal protein Thy-1 binds to αvß3 integrin in astrocytes, thereby leading to intricate signaling pathways that include calcium (Ca2+) release from intracellular stores, opening of Cx43 hemichannels, release of ATP, activation of P2X7 receptor, and Ca2+ influx. However, because these Thy-1 effects occur exclusively in reactive astrocytes, we wondered whether by elevating calcium levels and promoting hemichannel opening we could prompt non-reactive astrocytes to respond to Thy-1. Cx43 immunoreactivity increased at juxta-membrane sites, where hemichannels (not gap junctions) participate in astrocyte polarization and migration stimulated by Thy-1. Also, intracellular Ca2+ increase, due to ionomycin treatment, induced hemichannel opening, but activated astrocyte migration only partially, and this limitation was overcome by pre-treatment with tumor necrosis factor (TNF) and Thy-1. Finally, αvß3 integrin formed membrane clusters after TNF stimulation or overexpression of ß3 integrin. We suggest that these microclusters are required for cells to respond to Thy-1 stimulation. Therefore, the large increase in intracellular Ca2+ and hemichannel opening induced by ionomycin are required, but not sufficient, to permit Thy-1-induced astrocyte migration. Thus, we suggest that proinflammatory stimuli prompt astrocytes to respond to migratory signals of neuronal cells.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Astrócitos
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Cálcio
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Conexina 43
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Antígenos Thy-1
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Suíça