Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

Table 1

Palmitoylation sites and functions of neurotransmitter receptor palmitoylation.

Receptor type	Receptor subtype	Palmitoylation site	Palmitoylation function	Responsible DHHC	Reference
G protein-coupled receptors
Adrenergic	α1AR	C120	Receptor-mediated signaling and receptor expression	DHHC21	[58, 59]
	α2AR	Cys442	Receptor downregulation followed by chronic agonist exposure	Unknown	[54, 57]
	β2AR	Cys341	Receptor phosphorylation and β-arrestin binding; coupling to the AC-mediated signaling and desensitization		[8, 47, 49–51]
		Cys265	Receptor trafficking and localization	DHHC9, DHHC 14, DHHC 18
Serotonin	5-HT1A	Cys417, Cys420	Gi protein coupling/effector signaling, Gβγ-mediated signaling	Unknown	[66]
	5-HT4	Cys328, Cys329	Regulation of constitutive receptor activity	Unknown	[68]
	5-HT7	Cys404, Cys438, Cys441	Regulation of constitutive, Gs-mediated receptor activity	Unknown	[68, 75]
Dopamine	D1R	Cys347, Cys351	Receptor internalization and functional activity	Unknown	[93, 94]
	D2R	C443	Receptor surface expression and stability	DHHC3, DHHC8, DHHC4	[95–97]
	D3R	C400	Receptor localization on the plasma membrane, endocytosis, agonist binding	Unknown	[98]
	D4R	Cys467	Receptor cell surface expression, signaling and endocytosis	Unknown	[100]
Vasopressin	V1a	Cys371, Cys372	Receptor conformation and phosphorylation	Unknown	[108]
	V2R	Cys341, Cys342	Receptor trafficking and localization on the plasma membrane, agonist-dependent receptor sequestration/internalization, and endocytosis	Unknown	[109–111]
Adenosine	A(1)AR	Cys309	Receptor-effector coupling, agonist-induced internalization/downregulation	Unknown	[118]
	A2BAR	Cys311	Receptor conformation and interaction with different proteins related to sorting and signaling	Unknown	[121]
	A(3)AR	Cys305	Receptor recycling to the plasma membrane after agonist removal	Unknown	[119]
Opioid	μ-Opioid	C170	Receptor homodimerization and G protein coupling/activation	DHHC3, DHHC4	[126–128]
	δ-Opioid	Unknown	Receptor trafficking and/or localization	Unknown	[129]
Cannabinoid	CB(1)	Cys415	Receptor conformation, trafficking and localization	Unknown	[6, 136]
Acetylcholine	Muscarinic	Cys457	Receptor interaction with G protein	Unknown	[143]
Neuropeptide Y	Y(1)	Cys337	Receptor conformation, G protein coupling, desensitization	Unknown	[149]
Melatonin	MT(1), MT(2)	Cys7.72, Cys7.77	Receptor functioning toward cAMP inhibition	Unknown	[156]
Ligand-gated ion channels
Glutamate	NMDA	Cysteine clusters in the C-terminus of GluN2A and GluN2B subunits. The first cluster—GluN2A: C848, C853, and C870; and GluN2B: C849, C854, and C871. The second cluster—GluN2A: C1214, C1217, C1236, and C1239; and GluN2B: C1215, C1218, C1239, C1242, and C1245	Receptor retention in the Golgi apparatus, trafficking and surface expression/internalization	DHHC3	[4, 176, 177]
	AMPA	C610, C836	Subunit-specific receptors regulation and trafficking	DHHC2, DHHC3	[170, 172, 202]
	Kainate	C827 and C840	Receptor insertion and stabilization at the cell surface	Unknown	[178, 179]
GABA	GABAA	Multiple cysteine residues within the major intracellular domain of gamma2 subunit	Synaptic clustering of receptor, cell surface expression, and trafficking	DHHC3, DHHC7	[187–189]
Acetylcholine	Nicotinic α4	Cys273	Receptor total and cell surface expression	Unknown	[197]
Adenosine	P2X7	Cys371, 373, 374, 477, 479, 482, 498, 499, 506, 572, 573	Receptor trafficking and plasma membrane localization; receptor macromolecular organization	Unknown	[200]