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P2Y nucleotide receptor interaction with alpha integrin mediates astrocyte migration.
Min Wang1, Qiongman Kong, Fernando A Gonzalez
1Interdisciplinary Neuroscience Program, University of Missouri-Columbia, Missouri 65211, USA.
Journal of Neurochemistry
|September 2, 2005
Summary
Activation of P2Y(2) receptors by UTP in astrocytes increases glial fibrillary acidic protein (GFAP) expression and cell migration. This P2Y(2)R signaling pathway, involving alpha(V) integrins and PI3-K/Akt/MEK/ERK, is crucial for astrogliosis in brain disorders.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Astrocytes are key glial cells in the central nervous system.
- Astrocyte activation, marked by GFAP expression and proliferation, is a hallmark of brain injury.
- Extracellular nucleotides released during brain damage activate P2 nucleotide receptors.
Purpose of the Study:
- To investigate the role of P2Y(2) nucleotide receptors (P2Y(2)R) in astrocyte activation and migration.
- To elucidate the signaling pathways involved in P2Y(2)R-mediated astrocyte responses.
Main Methods:
- Primary rat astrocytes were used.
- Glial fibrillary acidic protein (GFAP) expression was measured.
- Astrocyte migration (chemotaxis and chemokinesis) was assessed.
- P2Y(2)R expression was silenced using siRNA.
- Integrin expression and function were analyzed.
- Western blotting was used to examine signaling pathway activation (PI3-K/Akt, MEK/ERK).
Main Results:
- Activation of P2Y(2)R by UTP increased GFAP expression and astrocyte migration.
- Silencing P2Y(2)R with siRNA inhibited UTP-induced migration.
- UTP increased alpha(V)beta(3/5) integrin expression, and anti-alpha(V) antibodies blocked UTP-stimulated migration.
- P2Y(2)R-mediated migration required activation of PI3-K/Akt and MEK/ERK signaling pathways, which were also inhibited by anti-alpha(V) integrin antibodies.
Conclusions:
- P2Y(2) nucleotide receptors play a significant role in regulating astrocyte activation and migration.
- The P2Y(2)R/alpha(V) integrin interaction is critical for UTP-induced astrocyte responses.
- PI3-K/Akt and MEK/ERK signaling pathways are essential for P2Y(2)R-mediated astrogliosis.
- P2Y(2)Rs represent potential therapeutic targets for managing astrogliosis in brain disorders.