Palmitoylation of nicotinic acetylcholine receptors.
It is well established that nicotinic acetylcholine receptors (nAChRs) undergo a number of different posttranslational modifications, such as disulfide bond formation, glycosylation, and phosphorylation. Recently, our laboratory has developed more sensitive assays of protein palmitoylation that have allowed us and others to detect the palmitoylation of relatively low abundant proteins such as ligand-gated ion channels. Here, we present evidence that palmitoylation is prevalent on many subunits of different nAChR subtypes, both muscle-type nAChRs and the neuronal "alpha(4)beta(2)" and "alpha(7)" subtypes most abundant in brain. The loss of ligand binding sites that occurs when palmitoylation is blocked with the inhibitor bromopalmitate suggests that palmitoylation of alpha(4)beta(2) and alpha(7) subtypes occurs during subunit assembly and regulates the formation of ligand binding sites. However, additional experiments are needed to test whether nAChR subunit palmitoylation is involved in other aspects of nAChR trafficking or whether palmitoylation regulates nAChR function. Further investigation would be aided by identifying the sites of palmitoylation on the subunits, and here we propose a mass spectrometry strategy for identification of these sites.
Alexander
J K
JK
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.
Govind
A P
AP
Drisdel
R C
RC
Blanton
M P
MP
Vallejo
Y
Y
Lam
T T
TT
Green
W N
WN
D000109:Acetylcholine / Q000378:metabolism; D000215:Acylation / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001681:Biological Assay / Q000379:methods; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D004557:Electric Organ / Q000378:metabolism; D006801:Humans; D008024:Ligands; D054878:Lipoylation / Q000502:physiology*; D013058:Mass Spectrometry / Q000379:methods; D009469:Neuromuscular Junction / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014101:Torpedo; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D008024:Ligands; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine
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