Immunoglobulin Fcγ receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

• Published in: Journal of neuroscience research Vol. 69; no. 1; pp. 110 - 116
• Main Authors: Mohamed, Habib A., Mosier, Dennis R., Zou, Ling L., Siklós, László, Alexianu, Maria E., Engelhardt, Jozsef I., Beers, David R., Le, Wei-dong, Appel, Stanley H.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.07.2002
• Subjects: Acetylcholine - biosynthesis; Acetylcholine - secretion; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Animals; Calcium - metabolism; Fc receptor; Female; Humans; immunoglobulin G; Immunoglobulin G - metabolism; Immunoglobulins - metabolism; Immunoglobulins - physiology; intracellular calcium; Intracellular Fluid - secretion; Life Sciences (General); Male; Mice; Mice, Inbred C57BL; Mice, Knockout; motoneuron; Motor Neurons - cytology; Motor Neurons - metabolism; Motor Neurons - secretion; Neuromuscular Junction - secretion; Neurotransmitter Agents - biosynthesis; Neurotransmitter Agents - secretion; Receptors, IgG - deficiency; Receptors, IgG - genetics; Receptors, IgG - physiology; Space life sciences; Non-Nasa Center; Nasa Discipline Musculoskeletal; NASA Discipline Musculoskeletal; Non-NASA Center
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10271

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. Copyright 2002 Wiley-Liss, Inc.