Gγ13 interacts with PDZ domain-containing proteins

Zairong Li, Outhiriaradjou Benard, Robert F. Margolskee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The G protein γ13 subunit (Gγ13) is expressed in taste and retinal and neuronal tissues and plays a key role in taste transduction. We identified PSD95, Veli-2, and other PDZ domain-containing proteins as binding partners for Gγ13 by yeast two-hybrid and pull-down assays. In two-hybrid assays, Gγ13 interacted specifically with the third PDZ domain of PSD95, the sole PDZ domain of Veli-2, and the third PDZ domain of SAP97, a PSD95-related protein. Gγ13 did not interact with the other PDZ domains of PSD95. Coexpression of Gγ13 with its Gβ1 partner did not interfere with these two-hybrid interactions. The physical interaction of Gγ13 with PSD95 in the cellular milieu was confirmed in pull-down assays following heterologous expression in HEK293 cells. The interaction of Gγ13 with the PDZ domain of PSD95 was via the C-terminal CAAX tail of Gγ13 (where AA indicates the aliphatic amino acid); alanine substitution of the CTAL sequence at the C terminus of Gγ13 abolished its interactions with PSD95 in two-hybrid and pull-down assays. Veli-2 and SAP97 were identified in taste tissue and in Gγ13-expressing taste cells. Coimmunoprecipitation of Gγ13 and PSD95 from brain and of Gγ13 and SAP97 from taste tissue indicates that Gγ13 interacts with these proteins endogenously. This is the first demonstration that PDZ domain proteins interact with heterotrimeric G proteins via the CAAX tail of Gγ subunits. The interaction of Gγ13 with PDZ domain-containing proteins may provide a means to target particular Gβγ subunits to specific subcellular locations and/or macromolecular complexes involved in signaling pathways.

Original languageEnglish (US)
Pages (from-to)11066-11073
Number of pages8
JournalJournal of Biological Chemistry
Issue number16
StatePublished - Apr 21 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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