A Highly Conserved Cytoplasmic Cysteine Residue in the α4 Nicotinic Acetylcholine Receptor Is Palmitoylated and Regulates Protein Expression

Abstract

Background:The mechanisms underlying nicotinic acetylcholine receptor (nAChR) trafficking are unclear. Results: Cysteine mutations within cytoplasmic loops of the ␣4 nAChR subunit change surface and total receptor expression, and a cysteine in the first loop is palmitoylated. Conclusion: ␣4 nAChR intracellular cysteines influence receptor stability and trafficking. Significance: Identifying the determinants of nAChR trafficking will provide insight into nAChR biology.

Nicotinic acetylcholine receptor–lipid interactions: Mechanistic insight and biological function

“…Although many factors are known to influence mammalian nAChR trafficking [129][130][131] (see also [132]), a role for M4 binding to M1/M3 has been clearly demonstrated in the homologous glycine receptor. When expressed in oocytes, the glycine receptor is cleaved within the intracellular loop, but still undergoes agonist-induced channel gating.…”

The role of the M4 lipid-sensor in the folding, trafficking, and allosteric modulation of nicotinic acetylcholine receptors

“…(Amici et al, 2012;Beeson et al, 2003;Tsetlin et al, 2011). Considerable evidence also suggests an important role for M4.…”

Roles of nicotinic acetylcholine receptor β subunit cytoplasmic loops in acute desensitization and single-channel features

“…Thus, differences between studies could reflect subunit sequence differences. Additionally, most above studies used outside-out patch recording, whereas we used the cell-attach technique, and there is the formal possibility that interactions with cytoplasmic or cytoskeletal elements could alter channel properties (Janmey, 1998, Akk and Steinbach, 2000, Amici et al, 2012), especially given that our studies show effects of substitution of nested C2 sequences expected to be quite remote from channel and nicotinic ligand binding domains but are candidates for cytoskeletal/cytoplasmic protein interactions. Consequently, we can attribute differences between studies to differences in the potential for such interactions due to the patch-clamp recording configuration used.…”