title: alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction.
abstract: Neurotransmission at chemical synapses of the brain involves alpha-neurexins, neuron-specific cell-surface molecules that are encoded by three genes in mammals. Deletion of alpha-neurexins in mice previously demonstrated an essential function, leading to early postnatal death of many double-knockout mice and all triple mutants. Neurotransmitter release at central synapses of newborn knockouts was severely reduced, a function of alpha-neurexins that requires their extracellular sequences. Here, we investigated the role of alpha-neurexins at neuromuscular junctions, presynaptic terminals that lack a neuronal postsynaptic partner, addressing an important question because the function of neurexins was hypothesized to involve cell-adhesion complexes between neurons. Using systems physiology, morphological analyses and electrophysiological recordings, we show that quantal content, i.e. the number of acetylcholine quanta released per nerve impulse from motor nerve terminals, and frequency of spontaneous miniature endplate potentials at the slow-twitch soleus muscle are reduced in adult alpha-neurexin double-knockouts, consistent with earlier data on central synapses. However, the same parameters at diaphragm muscle neuromuscular junctions showed no difference in basal neurotransmission. To reconcile these observations, we tested the capability of control and alpha-neurexin-deficient diaphragm neuromuscular junctions to compensate for an experimental reduction of postsynaptic acetylcholine receptors by a compensatory increase of presynaptic release: Knockout neuromuscular junctions produced significantly less upregulation of quantal content than synapses from control mice. Our data suggest that alpha-neurexins are required for efficient neurotransmitter release at neuromuscular junctions, and that they may perform a role in the molecular mechanism of synaptic homeostasis at these peripheral synapses.
authors.affiliation: Center for Physiology and Pathophysiology, Georg-August University, Humboldtallee 23, 37073 Göttingen, Germany.
authors.forename: M S
authors.initials: MS
authors.lastname: Sons
authors.forename: N
authors.initials: N
authors.lastname: Busche
authors.forename: N
authors.initials: N
authors.lastname: Strenzke
authors.forename: T
authors.initials: T
authors.lastname: Moser
authors.forename: U
authors.initials: U
authors.lastname: Ernsberger
authors.forename: F C
authors.initials: FC
authors.lastname: Mooren
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: H
authors.initials: H
authors.lastname: Steffens
authors.forename: E D
authors.initials: ED
authors.lastname: Schomburg
authors.forename: J J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: M
authors.initials: M
authors.lastname: Missler
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000294:innervation; D004195:Disease Models, Animal; D004594:Electrophysiology / Q000379:methods; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D009157:Myasthenia Gravis / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D017933:Peripheral Nervous System / Q000502:physiology / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins