Abstract
While muscle fibers are ensheathed in basement membrane material, the extracellular matrix at their synaptic segment, the neuromuscular junction (NMJ), is specialized and contains factors that are essential for the proper development, maintenance, and regeneration of the synapse after injury. Immunohistochemical studies have been critical in characterizing the composition of the synaptic basal lamina at the NMJ. Although NMJs are extremely stable synapses, they can undergo structural alteration both pre- and postsynaptically, especially during development and in response to injury. Even though there are no permanent molecular markers currently known for synaptic sites that have undergone elimination or remodeling, the relatively stable and specialized nature of the synaptic basal laminar components—which aided in their initial identification and characterization—makes them excellent markers for identification of recently eliminated synaptic sites and as ultrastructural indicators of morphological alterations of cellular synaptic components.
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References
Bowman W (1840) On the minute structure and movements of voluntary muscle. Phil Trans R Soc Lond 130:457–501
Patton BL (2000) Laminins of the neuromuscular system. Microsc Res Tech 51(3):247–261
Patton BL (2003) Basal lamina and the organization of neuromuscular synapses. J Neurocytol 32(5–8):883–903
Sanes JR (2003) The basement membrane/basal lamina of skeletal muscle. J Biol Chem 278(15):12601–12604
Singhal N, Martin PT (2011) Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction. Dev Neurobiol 71(11):982–1005
Li Y, Lee Y, Thompson WJ (2011) Changes in aging mouse neuromuscular junctions are explained by degeneration and regeneration of muscle fiber segments at the synapse. J Neurosci 31(42):14910–14919
Burden SJ, Sargent PB, McMahan UJ (1979) Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve. J Cell Biol 82(2):412–425
Marshall LM, Sanes JR, McMahan UJ (1977) Reinnervation of original synaptic sites on muscle fiber basement membrane after disruption of the muscle cells. Proc Natl Acad Sci U S A 74(7):3073–3077
Sanes JR, Marshall LM, McMahan UJ (1978) Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. J Cell Biol 78(1):176–198
McMahan UJ (1990) The agrin hypothesis. In: McMahan UJ (ed) Cold Spring Harbor symposia on quantitative biology, vol LV, The brain. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 407–418
McMahan UJ, Sanes JR, Marshall LM (1978) Cholinesterase is associated with the basal lamina at the neuromuscular junction. Nature 271(5641):172–174
Fox MA, Ho MS, Smyth N et al (2008) A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction. Neural Dev 3:24
Fox MA, Sanes JR, Borza DB et al (2007) Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals. Cell 129(1):179–193
Latvanlehto A, Fox MA, Sormunen R et al (2010) Muscle-derived collagen XIII regulates maturation of the skeletal neuromuscular junction. J Neurosci 30(37):12230–12241
Rosenberry TL, Rabl C-R, Neumann E (1996) Binding of the neurotoxin fasciculin 2 to the acetylcholinesterase peripheral site drastically reduces the association and dissociation rate constants for N-methylacridinium binding to the active site. Biochemistry 35(3):685–690
Peng HB, Xie H, Rossi SG et al (1999) Acetylcholinesterase clustering at the neuromuscular junction involves perlecan and dystroglycan. J Cell Biol 145(4):911–921
Anderson MJ, Cohen MW (1974) Fluorescent staining of acetylcholine receptors in vertebrate skeletal muscle. J Physiol 237(2):385–400
Culican SM, Nelson CC, Lichtman JW (1998) Axon withdrawal during synapse elimination at the neuromuscular junction is accompanied by disassembly of the postsynaptic specialization and withdrawal of Schwann cell processes. J Neurosci 18(13):4953–4965
Rodriguez-Ithurralde D, Silveira R, Barbeito L et al (1983) Fasciculin, a powerful anticholinesterase polypeptide from Dendroaspis angusticeps venom. Neurochem Int 5(3):267–274
Sugiyama J, Bowen DC, Hall ZW (1994) Dystroglycan binds nerve and muscle agrin. Neuron 13(1):103–115
Sasaki T, Mann K, Miner JH et al (2002) Domain IV of mouse laminin beta1 and beta2 chains. Eur J Biochem 269(2):431–442
Harris KM, Perry E, Bourne J et al (2006) Uniform serial sectioning for transmission electron microscopy. J Neurosci 26(47):12101–12103
Ferns M, Hoch W, Campanelli JT et al (1992) RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes. Neuron 8(6):1079–1086
Hoch W, Ferns M, Campanelli JT et al (1993) Developmental regulation of highly active alternatively spliced forms of agrin. Neuron 11(3):479–490
Balice-Gordon RJ, Lichtman JW (1993) In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions. J Neurosci 13(2):834–855
Yang JF, Cao G, Koirala S et al (2001) Schwann cells express active agrin and enhance aggregation of acetylcholine receptors on muscle fibers. J Neurosci 21(24):9572–9584
Acknowledgment
We thank Drs. Michael Ferns (the University of California, Davis) and Sasako Takaki (Friedrich-Alexander University, Erlangen, Germany) for their generous gifts of anti-agrin and anti-laminin-β2 antibodies, respectively. We are also grateful to Dr. Richard Rotundo (University of Miami) for sharing with us his protocol for fluorescence conjugation of the toxin, fasciculin 2. We also thank Dr. Wesley Thompson (Texas A&M University) for helpful comments on the manuscript and Michelle Mikesh (the University of Texas, Austin) for her assistance with EM tissue preparation.
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Lee, Y.i., Li, Y. (2015). The Use of Synaptic Basal Lamina and Its Components to Identify Sites of Recent Morphological Alterations at Mammalian Neuromuscular Junctions. In: Leach, J., Powell, E. (eds) Extracellular Matrix. Neuromethods, vol 93. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2083-9_2
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DOI: https://doi.org/10.1007/978-1-4939-2083-9_2
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