P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2

Sami R. Fam, Maryse Paquet, Amanda M. Castleberry, Heide Oller, C. Justin Lee, Stephen F. Traynelis, Yoland Smith, C. Chris Yun, Randy A. Hall

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

P2Y1 purinergic receptors (P2Y1Rs) mediate rises in intracellular Ca2+ in response to ATP, but the duration and characteristics of this Ca2+ response are known to vary markedly in distinct cell types. We screened the P2Y1R carboxyl terminus against a recently created proteomic array of PDZ (PSD-95/Drosophila Discs large/ZO-1 homology) domains and identified a previously unrecognized, specific interaction with the second PDZ domain of the scaffold NHERF-2 (Na+/H + exchanger regulatory factor type 2). Furthermore, we found that P2Y1R and NHERF-2 associate in cells, allowing NHERF-2-mediated tethering of P2Y1R to key downstream effectors such as phospholipase Cβ. Finally, we found that coexpression of P2Y1R with NHERF-2 in glial cells prolongs P2Y1R-mediated Ca2+ signaling, whereas disruption of the P2Y1R-NHERF-2 interaction by point mutations attenuates the duration of P2Y1R-mediated Ca2+ responses. These findings reveal that NHERF-2 is a key regulator of the cellular activity of P2Y1R and may therefore determine cell-specific differences in P2Y1R-mediated signaling.

Original languageEnglish
Pages (from-to)8042-8047
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number22
DOIs
Publication statusPublished - 2005 May 31

Keywords

  • ATP
  • G protein-coupled receptor
  • Proteomic array
  • Purinergic

ASJC Scopus subject areas

  • General

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    Fam, S. R., Paquet, M., Castleberry, A. M., Oller, H., Lee, C. J., Traynelis, S. F., Smith, Y., Yun, C. C., & Hall, R. A. (2005). P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. Proceedings of the National Academy of Sciences of the United States of America, 102(22), 8042-8047. https://doi.org/10.1073/pnas.0408818102