Antibody induced internalization of acetylcholine nicotinic receptor: kinetics, mechanism and selectivity.
The loss from the cell surface of cholinergic nicotinic receptors induced by exposure to antireceptor antibodies, and the mechanism of this loss has been studied in the BC3H-1 cell line. The maximal effect, i.e. 50% loss of receptors, was observed after 30 min. Receptor loss was due to internalization, which was not accompanied by a detectable increase in fluid phase endocytosis nor by changes in the number and distribution of intramembrane particles (IMP) revealed by freeze-fracture of the plasmalemma. The internalization was specific since the concentration of other receptors exposed at the surface of BC3H-1 cells (alpha and beta adrenergic receptors) was not affected by anticholinergic antibodies. It was temperature-dependent, independent of external calcium, but was blocked by trifluoperazine (TFP), a calmodulin antagonist. The rate of antibodies-induced receptor internalization was much more rapid than that of degradation and furthermore low concentrations of antibodies increased receptor internalization but did not increase receptor degradation. Our findings may be relevant to the clarification of the mechanism of Ab-induced alteration in autoimmune diseases, and in particular in myasthenia gravis.
Clementi
F
F
Sher
E
E
D000818:Animals; D000906:Antibodies; D002038:Bungarotoxins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005614:Freeze Fracturing; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism*; D011206:Povidone-Iodine / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D002038:Bungarotoxins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011978:Receptors, Nicotinic; D011206:Povidone-Iodine