Early events in neuromuscular junction formation in vitro: induction of acetylcholine receptor clusters in the postsynaptic membrane and morphology of newly formed synapses.

Frank, Eric; Fischbach, Gerald D.

doi:10.1083/jcb.83.1.143

Cited by 346 publications

(142 citation statements)

References 45 publications

(53 reference statements)

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“…In agreement with published results, α-Bgtx labeling of muscle nAChRs was observed under the same labeling conditions for hair cells at the NMJ (Fig. 4c) (Clarke, 1992;Frank and Fischbach, 1979). The α-Bgtx labeled clusters at the NMJ were two to three times larger than those on hair cells.…”

Section: Rapsyn and Ric-3 Localization And α-Bungarotoxin Labelingsupporting

confidence: 80%

Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear

Osman

Schrader

Hawkes

et al. 2008

Molecular and Cellular Neuroscience

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Nothing is known about the regulation of nicotinic acetylcholine receptors (nAChRs) in hair cells of the inner ear. MuSK, rapsyn and RIC-3 are accessory molecules associated with muscle and brain nAChR function. We demonstrate that these accessory molecules are expressed in the inner ear raising the possibility of a muscle-like mechanism for clustering and assembly of nAChRs in hair cells. We focused our investigations on rapsyn and RIC-3. Rapsyn interacts with the cytoplasmic loop of nAChR α9 subunits but not nAChR α10 subunits. Although rapsyn and RIC-3 increase nAChR α9 expression, rapsyn plays a greater role in receptor clustering while RIC-3 is important for acetylcholine-induced calcium responses. Our data suggest that RIC-3 facilitates receptor function, while rapsyn enhances receptor clustering at the cell surface.

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Section: Rapsyn and Ric-3 Localization And α-Bungarotoxin Labelingsupporting

confidence: 80%

Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear

Osman

Schrader

Hawkes

et al. 2008

Molecular and Cellular Neuroscience

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“…Optimal responses were usually produced with 100-nA ejection pulses and 5-to 10-nA backing currents. These values are higher than those used with acetylcholine ionophoresis (10) (Fig. 1C), consistent with the presence of hot spots located different distances from the tip of the pipette.…”

Section: Methodssupporting

confidence: 67%

Rapid desensitization of glutamate receptors in vertebrate central neurons.

Trussell¹,

Thio²,

Zorumski³

et al. 1988

Proceedings of the National Academy of Sciences

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We have examined glutamate receptor desensitization in voltage-clamped embryonic chicken spinal cord neurons and postnatal rat hippocampal neurons maintained in culture. Rapid currents that rose in 0.8-3.6 msec were evoked when glutamate was ionophoresed with 0.5-to 1.0-msec pulses. With prolonged pulses or brief, repetitive pulses, glutamate-evoked currents decayed rapidly in a manner that was independent of holding potential. A similar desensitization occurred following close-range pressure ejection of glutamate. The rapid, desensitizing glutamate current exhibited a linear current-voltage relation and it was not blocked by 2-amino-5-phosphonovalerate, suggesting that it was mediated by N-methyl-D-aspartate-insensitive (G2) receptors. Desensitization of G2 receptors may be agonist-dependent: currents evoked by kainate, a selective G2 agonist, did not decay, whereas prior application of glutamate did reduce the size of kainate responses. The appearance of the rapid current depended critically on the position of the ionophoretic pipette. Such glutamate-receptor "hot spots" often corresponded to points of contact with neighboring neurites, which raises the possibility that they are located at synapses.Glutamate is considered to be a "mixed agonist" in that it activates more than one type of receptor. The most common classification of glutamate receptors is based on the relative efficacy of three agonists: N-methyl-D-aspartate (N-Me-DAsp), kainate, and quisqualate (1-4). In chicken spinal cord neurons, kainate and quisqualate appear to compete for the same site, so we refer to only two' broad categories (2): G1 receptors are activated by N-Me-D-Asp and blocked by 2-amino-5-phosphonovalerate (APV) and Mg2 + (the latter in a voltage-dependent manner); G2 receptors are activated by kainate and quisqualate. In addition, G1, but not G2, currents are desensitized following prolonged or repeated application of glutamate (or more selective agonists) over a period of several seconds (5).It is important to determine whether receptor desensitization occurs on the time scale of synaptic transmission. Our previous studies did not address this issue because the agonists were applied by pressure ejection from pipettes located 25-50 ,um away from the target neuron (2,5,6). In this situation, the buildup of agonist concentration at the receptor sites is slow compared to the time course of synaptically released transmitter. In addition, such a diffuse application must activate extrasynaptic as well as synaptic receptors.In this study, we examined rapid desensitization following focal ionophoresis or close-range pressure ejection of glutamate and other agonists. Responses evoked at extremely sensitive sites (hot spots) on the neuronal surface were desensitized rapidly. The desensitizing currents were not blocked by APV. These data suggest that G2 receptors are, in fact, desensitized but with a time course that is >2 orders of magnitude faster than G1 receptor desensitization. Some of these results have been presented in abst...

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“…These studies have revealed that competent neurons, such as motor neurons and other cholinergic neurons, trigger profound changes in the distribution of AChRs on the surface of the muscle cells they innervate. Following net&e-muscle contact, AChRs accumulate in high density along the path of contact, while elsewhere on the muscle cell the survival of preexisting AChR patches is reduced and the formation of new AChR patches inhibited Frank and Fischbach, 1979;Moody-Corbett and Cohen, 1982;Kuromi and Kidokoro, 1984). As a result, AChRs become localized preferentially at sites of innervation, thereby permitting efficient synaptic transmission.…”

mentioning

confidence: 99%

Distribution of synaptic specializations along isolated motor units formed in Xenopus nerve-muscle cultures

Cohen¹,

Rodriguez-Marin²,

Wilson³

1987

J. Neurosci.

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The capacity of individual muscle cells and neurons to establish synaptic specializations along the entire extent of their neurite- muscle contacts was assessed in culture. Spinal cord neurons derived from embryos of Xenopus laevis were plated at low density in cultures of Xenopus myotomal muscle cells in order to obtain isolated motor units whose neuron and muscle cells were not contacted by any other neuron. These isolated motor units were examined for localization of acetylcholine receptors (AChRs) after staining with fluorescent alpha- bungarotoxin and, in some cases, for localization of a synaptic vesicle antigen by immunofluorescence. The neurite-muscle contacts formed by competent neurons exhibited discontinuous sites of AChR localization occupying about 25% of the contact length as compared with 2% for incompetent neurons. Competent neurons, unlike incompetent ones, established these neurite-associated receptor patches (NARPs) on virtually all the muscle cells they contacted and functionally innervated them. These and other observations on the distribution of NARPs throughout the isolated motor units indicate that the capacity of competent neurons to establish NARPs extends to the limits of growth of most if not all of their neurites, that this capacity is least in the most proximal portions of initial neuritic segments, and that the overall capacity of muscle cells to generate NARPs can be saturated by long lengths of neurite-muscle contact. The results also suggest that even in the absence of competitive interactions between neurons there are spatial discontinuities in neuritic action and/or muscle response during the establishment of NARPs. Synaptic vesicle antigen patches (SVAPs) occurred along the neuritic arbor of all neurons, but their distribution in competent neurons (those which established NARPs) and in incompetent ones differed. For competent neurons the percentage of neurite length occupied by SVAPs was 4.8-fold greater on muscle cells than off, whereas the corresponding value for incompetent neurons was only 1.5-fold. This large preferential localization of SVAPs along neurite-muscle contacts of competent neurons was further associated with a colocalization of SVAPs and NARPs that was greater than predicted by chance. These results suggest that muscle cells are much more effective in influencing the distribution of synaptic vesicles along the neuritic arbor of competent neurons than along the arbor of incompetent neurons and that this influence is greatest at sites of postsynaptic differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

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Early events in neuromuscular junction formation in vitro: induction of acetylcholine receptor clusters in the postsynaptic membrane and morphology of newly formed synapses.

Cited by 346 publications

References 45 publications

Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear

Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear

Rapid desensitization of glutamate receptors in vertebrate central neurons.

Distribution of synaptic specializations along isolated motor units formed in Xenopus nerve-muscle cultures

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