The roles played by highly truncated splice variants of G protein-coupled receptors

Wise, Helen

doi:10.1186/1750-2187-7-13

Journal of Molecular Signaling

Table 1 GPCR splice variants with altered or deleted transmembrane domains

From: The roles played by highly truncated splice variants of G protein-coupled receptors

Receptor	Splicing consequence	General properties of splice variant	Dom/neg?	Refs.
α_1A-adrenoceptor	Truncated 6TM mutants.	No cell surface expression.	Yes	[28]
Calcitonin receptor (CT receptor)	Truncated 6TM mutant.	Rabbit CTRΔe13 is poorly expressed on the cell surface and fails to activate cell signaling.	Yes	[29]
Chemokine receptor 5 (CCR5)	Severely truncated mutants. Ccr5Δ32 is a 5TM mutant.	Natural mutants of human chemokine receptor CCR5 lacking the last 3 or 5 TMDs are non-functional. Ccr5Δ32 complexes with CCR5 and retains CCR5 in the ER, thus reducing cell surface expression.	Yes	[30, 31]
Dopamine receptor (D₃)	D3nf is a truncated 5TM mutant.	Human D3nf mutant has a punctuate perinuclear distribution and does not bind DA-ligands.	Yes	[32, 33]
GABA_B receptor (GABA_BR1)	GABA_BR1c has an additional 31 amino acids in TM5.		No	[34]
Gastric inhibitory polypeptide receptor (GIP )	Truncated 4TM mutant.	This inactive mutant receptor inhibited GIP signaling and decreased cell surface expression by retaining WT receptor in the ER.	Yes	[35]
Ghrelin receptor (or GHS-R1a)	GHS-R1b is a truncated 5TM mutant.	GHS-R1b is a non-signaling splice variant of GHS-R1a.	Yes	[36]
Gonadotropin-releasing hormone receptor (GnRH receptor)	Truncated 5TM mutant.	5TM variant of human GnRH receptor shows decreased cell surface expression, no ligand binding and no signal transduction.	Yes	[37]
Growth hormone-releasing hormone receptor (GHRH-R)	Truncated 5TM mutant.	The mutant GHRH-R cannot transduce GHRH signals.	Yes	[38]
Histamine receptor (H₃)	6TM-rH₃R is a truncated 6TM mutant.	Several splice variants of rat H₃R do not bind agonist, have an intracellular localization and co-expression with WT receptor decreases cell surface expression and functional responses.	Yes	[39]
Histamine receptor (H₄)	hH₄R(302) lacks 88 amino acids from TMD2 to TMD4. hH₄R(67) is a ~ 1.5TM truncated mutant.	These human H₄R splice variants were localised predominantly intracellularly when expressed in recombinant cells. No ligand binding or cell signaling detected.	Yes	[40]
Leukotriene B₄ receptor (BLT₁)	LTB4R-AS1 lacks TMD2 and part of ECL1 (39 amino acid deletion).	Both isoforms of human BLT₁ (LTB4R) are expressed in human airway smooth muscle cells.	Yes	[41]
Leukotriene B₄ receptor (BLT₁)	LTB4R-AS2 is the 3TMD to C-terminus (lacks 100 amino acids).		Yes	[41]
Luteinizing hormone receptor (LH receptor)	Truncated 5TM mutant.	The 5TM mutant of human LH receptor binds ligand (limited) but has no signaling activity.	Yes	[42]
μ-opioid receptor (μ-OR)	Truncated 6TM mutant.	A 6TM μ-OR variant in mice identified ligands lacking the traditional side effects of classical opiates but maintaining analgesic property.	No	[6]
Motilin receptor	GPR38-B is a truncated 5TM mutant.		?	[43]
Neurokinin 2 receptor (NK₂)	An ICL2-TM4 deletion mutant.	NK₂β splice variant is poorly expressed on the cell membrane and is non-signaling.	Yes	[44]
Neuropeptide Y receptor (Y₁)	A truncated 5TM mutant.	The putative hY₁-related 5TM accessory protein encoded by the non-spliced hY1 mRNA is not involved in facilitating hY₁ production.	No	[13]
Neurotensin receptor (NTS₂)	Truncated 5TM mutant with long tail.	Rat vNTS₂ is functionally active and can heterodimerize with NTS₂.	No	[45]
Nociceptin receptor (NOP)	Truncated 4TM mutant.	The rat truncated NOP receptor is localised to cell membranes but is non-functional.	Yes	[46]
Prostaglandin F_2α receptor (FP)	A 6TM truncated mutant (FP_s)	hFP_S is functionally inactive and highly expressed in the perinuclear region.	Yes	[47]
Prostaglandin F_2α receptor (FP)	A truncated mutant (PTGFR-v2).	No distinct functional role identified.	No	[48]
Somatostatin receptor (sst₅)	Human sst5TMD5 is a 5TM truncated mutant.	Identified novel truncated but functional human sst₅-variants; present in normal and tumoral tissues.	No	[49]
	Human SST5TMD4 is a 4TM truncated mutant.		No	[49]
	Murine sst5TMD4 is a 4TM truncated mutant.	Three murine variants were functional to mediate ligand-selective-induced variations in Ca²⁺ and cAMP despite being truncated and displayed a preferential intracellular distribution.	No	[50]
	Murine sst5TM2 is a 2TM truncated mutant.
	Murine and rat sst5TM1 has just TM1.
Vasopressin receptor, subtype 2 (V₂)	V₂b is a truncated 6TM mutant.	V₂b is retained in the ER where its C-terminus can be either intracellular or extracellular.	Yes	[51]

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