Table 1.

Functional role of known PDZ protein interactions with GPCRs

PDZ protein	GPCR	Reported effect on GPCR	Reference
CAL	β1AR	↓ membrane expression	He et al., 2004
(PIST, GOPC, FIG)	mGluR1a	Agonist-induced intracellular co-localization with receptor, ↓ ERK activation	Zhang et al., 2008
	mGluR5a	↑ mGluR5a protein expression, ↓ receptor ubiquitination	Cheng et al., 2010
	SSTR5	Targets receptor to Golgi apparatus (agonist-independent), ↓ membrane-targeting/recycling	Wente et al., 2005
GIPC	β1AR	↓ ERK activation, no effect on cAMP signalling	Hu et al., 2003
(TIP-2, Synectin)	D2	Targets receptor to Golgi region	Jeanneteau et al., 2004
	D3	↓ signal transduction through Gi, targets receptor to Golgi region, ↓ D3 degradation	Jeanneteau et al., 2004
	hLHR	Maintains receptor cell surface expression during hormone internalization	Hirakawa et al., 2003
MAGI-2	β1AR	↑ agonist-induced internalization, no effect on cAMP signalling	Xu et al., 2001
(S-SCAM, ARIP-1)	VPAC1	↓ cAMP signalling, ↓ agonist-induced internalization	Gee et al., 2009
MAGI-3	β1AR	↓ ERK activation	He et al., 2006
	β2AR	↓ ERK activation	Yang et al., 2010b
	LPA2	↑ ERK activation, ↑ RhoA activation	Zhang et al., 2007
MPP3	5-HT2c	↑ membrane stability, ↓desensitization	Gavarini et al., 2006
MUPP-1	5-HT2a	↑ localization to cell surface	Jones et al., 2009
	GABAB	↑ Ca2+ signalling	Balasubramanian et al., 2007
	MT1	↑ coupling with Gi protein, ↑ inhibition of adenylyl cyclase activity	Guillaume et al., 2008
	OR2AG1	Modulates Ca2+ signalling	Dooley et al., 2009
NHERF1	5-HT4a	Targets receptor to microvilli to interact with ezrin (potential role in cytoskeletal remodelling)	Joubert et al., 2004
(EBP50)	β2AR	Agonist-induced co-localization with receptor	Hall et al., 1998
	β2AR	Regulates receptor sorting through ERM-binding domain interactions	Cao et al., 1999
	hKOR	↓ receptor down-regulation, ↑ recycling	Li et al., 2002
	PTH1R	↓ agonist-induced internalization, negligible effect on recycling and cAMP signalling	Wang et al., 2007
	PTH1R	↑ coupling to, and activation of, Gq	Wang et al., 2010
	PTH1R	↓ interaction with β-arrestin-2, ↓ desensitization	Wang et al., 2009
	PTH1R	Targets receptor to membrane regions in close proximity to cytoskeleton, ↑ cAMP signalling	Wheeler et al., 2008
	TPβ	↓ internalization	Rochdi and Parent, 2003
NHERF2	LPA2	↑ interaction with PLCβ3	Choi et al., 2010
(E3KARP, SIP-1, TKA-1)	LPA2	↑ IP3 signalling, ↑ ERK activation	Oh et al., 2004
	mGluR5a	↑ agonist-induced Ca2+ signalling	Paquet et al., 2006
	P2Y1R	↑ interaction with PLCβ, ↑ agonist-induced Ca2+ signalling	Fam et al., 2005
	PTH1R	↑ interaction with, and activates, PLCβ	Mahon et al., 2002
	PTH1R	↓ adenylyl cyclase activity through stimulation of inhibitory G-proteins (Gi/o proteins).	Mahon et al., 2002
	PTH1R	↑ coupling to, and activation of, Gq and Gi; ↓ coupling to, and activation of, Gs	Wang et al., 2010
PAR-3	BK	↑ interaction with PLCβ1	Choi et al., 2010
PDZ-GEF	β1AR	Required for agonist-induced Ras activation via Gs-mediated cAMP signalling	Pak et al., 2002
(CNrasGEF, RA-GEF, Rap GEP)
PICK1	mGluR7a	↓ PKCα-mediated receptor phosphorylation	Dev et al., 2000
	PrRP (GPR10)	↑ intracellular clustering of receptor	Lin et al., 2001
PSD-95	5-HT2a	↓ agonist-induced internalization, ↑ IP3 signalling	Xia et al., 2003b
(DLG4, SAP90)	5-HT2c	↑ constitutive and agonist-induced internalization, ↑ desensitization	Gavarini et al., 2006
	β1AR	↓ agonist-induced internalization, no effect on cAMP signalling	Hu et al., 2000
	D1	↑ constitutive internalization, ↓ cAMP signalling	Zhang et al., 2007
	D1	↑ recycling, ↑ resensitization, no effect on Gs activation or cAMP signalling	Sun et al., 2009
SAP97	β1AR	↑ PKA-mediated receptor phosphorylation, ↑ recycling	Gardner et al., 2007
(DLG1)
Tamalin	mGluR1a	↑ membrane expression, ↑ complex formation with cytohesin-2 (GEF)	Kitano et al., 2002
(GRASP)