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Caveolin‐1 Supports the P2Y 2 Receptor Signaling
Author(s) -
Martinez Namyr Antonio,
Ayala Alondra Mali,
Martinez Magdiel,
Quiñones Monica,
Miranda Jorge D.,
Silva Walter I.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.729.5
Subject(s) - extracellular , microbiology and biotechnology , intracellular , caveolin 1 , receptor , p2y receptor , caveolae , purinergic receptor , phosphorylation , cell signaling , biology , calcium signaling , caveolin , signal transduction , nucleotide , chemistry , biochemistry , gene
Damage to the CNS cells’ can cause a differential spatiotemporal release of multiple factors into the extracellular space. Among such factors, nucleotides, and their interaction with the P2Y 2 nucleotide receptors (P2Y 2 Rs) have gained prominence as putative modulators of gliotic responses after CNS injury. Yet, the molecular mechanisms underlying these interactions and responses remain to be explored. Discontinuous sucrose density gradient separation of 1321N1 cells (expressing recombinant hP2Y 2 R) homogenates revealed co‐fractionation of P2Y 2 Rs in cav‐1 (+) membrane‐raft fractions. Likewise, confocal microscopy revealed that a significant percent of P2Y 2 Rs co‐localized with cav‐1 in its sub‐cellular distribution. Blocking cav‐1 expression in hP2Y 2 ‐1321N1 cells elicited abnormal intracellular Ca 2+ mobilization responses and uncharacteristic patterns of AKT, ERK 1/2 and p38 phosphorylation levels when stimulated with nucleotide agonists, as determined by microfluorometric calcium imaging analyses and immunoblotting, respectively. Our findings suggest that P2Y 2 Rs reside in membrane caveolae of non‐stimulated 1321N1 cells and that this sub‐cellular compartment may couple its downstream signaling machinery. We hypothesize that P2Y 2 Rs’ signaling cascades are linked to their expression in cav‐1 (+) micro‐domains. NAM is supported by the NIGMS‐NIH award number R25GM061838 at the UPR‐MSC.