Loss of laminin-alpha4 results in pre- and postsynaptic modifications at the neuromuscular junction

Chand, Kirat K., Lee, Kah Meng, Lavidis, Nickolas A. and Noakes, P. G. (2016) Loss of laminin-alpha4 results in pre- and postsynaptic modifications at the neuromuscular junction. FASEB Journal, 31 4: 1323-1336. doi:10.1096/fj.201600899R


Author Chand, Kirat K.
Lee, Kah Meng
Lavidis, Nickolas A.
Noakes, P. G.
Title Loss of laminin-alpha4 results in pre- and postsynaptic modifications at the neuromuscular junction
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2016-12-20
Year available 2016
Sub-type Article (original research)
DOI 10.1096/fj.201600899R
Open Access Status Not yet assessed
Volume 31
Issue 4
Start page 1323
End page 1336
Total pages 14
Place of publication Bethesda, MD United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Subject 1305 Biotechnology
1303 Biochemistry
1312 Molecular Biology
1311 Genetics
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 in lama4(-/-) 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 of lama4(-/-) 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.
Formatted 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 lama4 gene does not alter gross NMJ morphogenesis. However, mice deficient in laminin-α4 (lama4−/−) 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 in lama4−/− and wild-type mice. Lama4−/− NMJs demonstrated a decrease in miniature end plate potential frequency and increased amplitude of miniature end plate potentials 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 of lama4−/− NMJs, where we see altered distribution of Bassoon, a molecular component of active zones presumably resulting from perturbed neurotransmission.
Keyword Basal lamina
Neuromuscular synapses
Neurotransmission
Skeletal muscle
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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