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

Sami R. Fam, Maryse Paquet, Amanda M. Castleberry, Heide Oller, Changjoon 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
Externally publishedYes

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Purinergic P2Y1 Receptors
PDZ Domains
Type C Phospholipases
Point Mutation
Neuroglia
Proteomics
Drosophila
sodium-hydrogen exchanger regulatory factor
Adenosine Triphosphate

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. / Fam, Sami R.; Paquet, Maryse; Castleberry, Amanda M.; Oller, Heide; Lee, Changjoon; Traynelis, Stephen F.; Smith, Yoland; Yun, C. Chris; Hall, Randy A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 22, 31.05.2005, p. 8042-8047.

Research output: Contribution to journalArticle

Fam, SR, Paquet, M, Castleberry, AM, Oller, H, Lee, C, Traynelis, SF, Smith, Y, Yun, CC & Hall, RA 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, vol. 102, no. 22, pp. 8042-8047. https://doi.org/10.1073/pnas.0408818102
Fam, Sami R. ; Paquet, Maryse ; Castleberry, Amanda M. ; Oller, Heide ; Lee, Changjoon ; Traynelis, Stephen F. ; Smith, Yoland ; Yun, C. Chris ; Hall, Randy A. / P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 22. pp. 8042-8047.
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