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Gα(q/11)‐coupled P2Y 2 nucleotide receptor inhibits human keratinocyte spreading and migration
Author(s) -
Taboubi Salma,
Milanini Julie,
Delamarre Estelle,
Parat Fabrice,
Garrouste Francoise,
Pommier Gilbert,
Takasaki Jun,
Hubaud JeanClaude,
Kovacic Herve,
Lehmann Maxime
Publication year - 2007
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/fj.06-7476com
Subject(s) - microbiology and biotechnology , autocrine signalling , keratinocyte , cell migration , lamellipodium , integrin , wound healing , rhoa , protein kinase b , focal adhesion , chemistry , rac1 , paracrine signalling , extracellular , mapk/erk pathway , receptor , signal transduction , biology , cell , biochemistry , immunology , in vitro
Reepithelialization is a critical step in wound healing. It is initiated by keratinocyte migration at the wound edges. After wounding, extracellular nucle‐otides are released by keratinocytes and other skin cells. Here, we report that activation of P2Y 2 nucleotide receptor by ATP/UTP inhibits keratinocyte cell spreading and induces lamellipodium withdrawal. Kymogra‐phy analysis demonstrates that these effects correlate with a durable decrease of lamellipodium dynamics. P2Y 2 receptor activation also induces a dramatic dismantling of the actin network, the loss of a3 integrin expression at the cell periphery, and the dissolution of focal contacts as indicated by the alteration of av integrins and focal contact protein distribution. In addition, activation of P2Y 2 R prevents growth factor‐induced phosphorylation of Erk 1,2 and Akt/PkB. The use of a specific pharmacological inhibitor (YM‐254890), the depletion of Ga( q / 11 ) by siRNA, or the expression of a constitutively active Ga( q / 11 ) mutant (Q209L) show that activation of Ga (q/11) is responsible for these ATP/ UTP‐induced effects. Finally, we report that ATP delays growth factor‐induced wound healing of keratino‐cyte monolayers. Collectively, these findings provide evidence for a unique and important role for extracellular nucleotides as efficient autocrine/paracrine regulators of keratinocyte shape and migration during wound healing.— Taboubi, S., Milanini, J., Delamarre, E., Parat, F., Garrouste, F., Pommier, G., Takasaki, J., Hubaud, J‐C., Kovacic, H., Lehmann, M. Ga(q/11)‐coupled P2Y2 Nucleotide Receptor Inhibits Human Keratinocyte Spreading and Migration. FASEB J . 21, 4047–4058 (2007)