title: Loss of laminin-α4 results in pre- and postsynaptic modifications at the neuromuscular junction.
abstract: Synaptic basal lamina such as laminin-421 (α4β2γ1) mediate differentiation of the neuromuscular junction (NMJ). Laminins interact with their pre- or postsynaptic receptors to provide stability and alignment of the pre- to postsynaptic specializations. Knockout of the laminin-α4 gene (lama4) does not alter gross NMJ morphogenesis. However, mice deficient in laminin-α4 (lama4-/-mice) display disruptions in the alignment of the active zones and postsynaptic folds at the NMJ, although the physiological consequences of this loss have not been examined. The present study investigated the differences in neurotransmission during the early development and maturation of the NMJ inlama4-/-and wild-type mice.Lama4-/-NMJs demonstrated a decrease in miniature end-plate potential (EPP) frequency and increased amplitude of miniature EPPs and evoked EPPs. Binomial parameters analysis of neurotransmitter release revealed a decrease in quantal release, the result of a decrease in the number of active release sites, but not in the probability of transmitter release.Lama4-/-NMJs displayed higher levels of synaptic depression under high-frequency stimulation and altered facilitation, suggesting compromised delivery of synaptic vesicles. This idea is supported by our molecular investigations oflama4-/-NMJs, where we see altered distribution of Bassoon, a molecular component of active zones, presumably resulting from perturbed neurotransmission.-Chand, K. K., Lee, K. M., Lavidis, N. A., Noakes, P. G. Loss of laminin-α4 results in pre- and postsynaptic modifications at the neuromuscular junction.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Kirat K
authors.initials: KK
authors.lastname: Chand
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Kah Meng
authors.initials: KM
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Nickolas A
authors.initials: NA
authors.lastname: Lavidis
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia; p.noakes@uq.edu.au.|Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055369:Miniature Postsynaptic Potentials; D009045:Motor Endplate / Q000378:metabolism* / Q000502:physiology
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin
keywords: basal lamina; neuromuscular synapses; neurotransmission; skeletal muscle