The immunocytochemical localization of N-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction.
Although glutamate is thought to be the neurotransmitter at the invertebrate neuromuscular junction, acetylcholine is accepted as the primary neurotransmitter of the vertebrate motoneurons. N-acetylaspartylglutamate, a dipeptide localized in putative glutamatergic neurons in brain, is also found in high concentrations (> mM) in mammalian motoneurons and the ventral roots of spinal cord. N-acetylaspartylglutamate, which is released from neurons by depolarization in a Ca(2+)-dependent fashion, is implicated in glutamatergic transmission in two ways: it is a partial agonist at NMDA receptors, and it is cleaved to yield extracellular glutamate and N-acetylasparate by the specific peptidase N-acetylated alpha-linked acidic dipeptidase. Given the localization of N-acetylaspartylglutamate in motor neuronal perikarya and axons, we wondered whether N-acetylaspartylglutamate or glutamate cleaved from N-acetylaspartylglutamate by N-acetylated alpha-linked acidic dipeptidase may also play a role in neuromuscular transmission. Here we describe the immunocytochemical detection at the rat neuromuscular junction of N-acetylaspartylglutamate in terminals of motoneurons, of N-acetylated alpha-linked acidic dipeptidase in perisynaptic Schwann cells, and of the NMDAR-1 glutamate receptor subunit on postsynaptic muscle membranes. These results point to a potential role for N-acetylaspartylglutamate at the rat neuromuscular junction. Further, this is the first demonstration of a glutamate receptor protein at vertebrate neuromuscular synapses. Together with other recent findings, our results suggest that glutamate-like molecules are involved in neuromuscular transmission not only in invertebrates but also in veretebrates where they may modulate signaling by acetylcholine.
Berger
U V
UV
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital East, Charlestown 02129, USA.
Carter
R E
RE
Coyle
J T
JT
D000818:Animals; D004150:Dipeptidases / Q000276:immunology* / Q000502:physiology; D004151:Dipeptides / Q000276:immunology* / Q000502:physiology; D043425:Glutamate Carboxypeptidase II; D007150:Immunohistochemistry; D009469:Neuromuscular Junction / Q000502:physiology*; D010791:Phrenic Nerve; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology* / Q000502:physiology; D014714:Vertebrates
D004151:Dipeptides; D016194:Receptors, N-Methyl-D-Aspartate; C027172:isospaglumic acid; D004150:Dipeptidases; D043425:Glutamate Carboxypeptidase II