Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons.
Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals.
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Habib A
HA
Mohamed
Dennis R
DR
Mosier
Ling L
LL
Zou
László
L
Siklós
Maria E
ME
Alexianu
Jozsef I
JI
Engelhardt
David R
DR
Beers
Wei-dong
WD
Le
Stanley H
SH
Appel
D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000378:metabolism*; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D007074:Immunoglobulin G; D007136:Immunoglobulins; D018377:Neurotransmitter Agents; D017452:Receptors, IgG; D000109:Acetylcholine; D002118:Calcium