Ceramides modulate cell-surface acetylcholine receptor levels.
The effects of ceramides (Cer) on the trafficking of the nicotinic acetylcholine receptor (AChR) to the plasma membrane were studied in CHO-K1/A5 cells, a clonal cell line that heterologously expresses the adult murine form of the receptor. When cells were incubated with short- (C6-Cer) or long- (brain-Cer) chain Cer at low concentrations, an increase in the number of cell-surface AChRs was observed concomitant with a decrease in intracellular receptor levels. The alteration in AChR distribution by low Cer treatment does not appear to be a general mechanism since the surface expression of the green fluorescent protein derivative of the vesicular stomatitis virus protein (VSVG-GFP) was not affected. High Cer concentrations caused the opposite effects, decreasing the number of cell-surface AChRs, which exhibited higher affinity for [125I]-alpha-bungarotoxin, and increasing the intracellular pool, which colocalized with trans-Golgi/TGN specific markers. The generation of endogenous Cer by sphingomyelinase treatment also decreased cell-surface AChR levels. These effects do not involve protein kinase C zeta or protein phosphatase 2A activation. Taken together, the results indicate that Cer modulate trafficking of AChRs to and stability at the cell surface.
Gallegos
C E
CE
UNESCO Chair of Biophysics and Molecular Neurobiology and Instituto de Investigaciones Bioquímicas de Bahía Blanca, Argentina.
Pediconi
M F
MF
Barrantes
F J
FJ
D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002518:Ceramides / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology
D002518:Ceramides; D011978:Receptors, Nicotinic; D009761:Nystatin; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine