Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes

Vernallis, Ann B.; Conroy, William G.; Berg, Daniela

doi:10.1016/0896-6273(93)90333-m

Cited by 293 publications

(231 citation statements)

References 37 publications

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“…1a). The N-terminus up to TM2 regulates intersubunit assembly into receptor complexes, and α7 subunits do not coassemble with nAChR subunits, as demonstrated for endogenous subunits in CG neurons and for chimeric α7 subunits expressed in Xenopus laevis oocytes 4,5,12,13 . In particular, we have observed that coexpression of chimeric α7 subunits containing the α3 cytoplasmic loop together with wild-type α3 and β4 subunits in Xenopus oocytes results in the formation of two distinct receptor types that have the pharmacological properties of Bgt-nAChRs and nAChRs, respectively (data not shown).…”

Section: Resultsmentioning

confidence: 91%

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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ResultsUsing PCR, we constructed chimeric subunits in which the α7 cytoplasmic loop immediately after TM3 and before TM4 was replaced with the homologous region of the α3 or α5 sequence (Fig. 1a). The N-terminus up to TM2 regulates intersubunit assembly into receptor complexes, and α7 subunits do not coassemble with nAChR subunits, as demonstrated for endogenous subunits in CG neurons and for chimeric α7 subunits expressed in Xenopus laevis oocytes 4,5,12,13 . In particular, we have observed that coexpression of chimeric α7 subunits containing the α3 cytoplasmic loop together with wild-type α3 and β4 subunits in Xenopus oocytes results in the formation of two distinct receptor types that have the pharmacological properties of Bgt-nAChRs and nAChRs, respectively (data not shown). Thus, a difference in the distribution of chimeric α7 as compared to wild-type α7 on the infected CG neuron surface would result from the added α3 or α5 cytoplasmic loop. It cannot be explained by assembly with an endogenous nAChR subunit that can target to the synapse. Different types of neurotransmitter receptors coexist within single neurons and must be targeted to discrete synaptic regions for proper function. In chick ciliary ganglion neurons, nicotinic acetylcholine receptors (nAChRs) containing α3 and α5 subunits are concentrated in the postsynaptic membrane, whereas α-bungarotoxin receptors composed of α7 subunits are localized perisynaptically and excluded from the synapse. Using retroviral vector-mediated gene transfer in vivo, we show that the long cytoplasmic loop of α3 targets chimeric α7 subunits to the synapse and reduces endogenous nAChR surface levels, whereas the α5 loop does neither. These results show that a particular domain of one subunit targets specific receptor subtypes to the interneuronal synapse in vivo. Moreover, our findings suggest a difference in the mechanisms that govern assembly of interneuronal synapses as compared to the neuromuscular junction in vertebrates.1998 Nature America Inc.• http://neurosci.nature.com 1998 Nature America Inc.• http://neurosci.nature.com

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Section: Resultsmentioning

confidence: 91%

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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“…1) either on the soma or on the spines (Jacob and Berg, 1983;Loring et al, 1985;Wison Horch and Sargent, 1995;Shoop et al, 1999Shoop et al, , 2002. PSDs on the neurons contain either heteromeric nicotinic receptors composed of ␣3, ␤4, ␣5, and sometimes ␤2 subunits (Jacob et al, 1984;Loring and Zigmond, 1987;Vernallis et al, 1993) or, alternatively, glycine receptors (Tsen et al, 2000). The fact that both the spines and PSDs are overlaid by a large vesicle-filled presynaptic calyx engulfing the ciliary neuron suggests that even "perisynaptic" ␣7-nAChRs, i.e.…”

Section: Postsynaptic/perisynaptic Sitesmentioning

confidence: 99%

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

2002

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Nicotinic receptors are cation-ion selective ligand-gated ion channels that are expressed throughout the nervous system. Most have significant calcium permeabilities, enabling them to regulate calcium-dependent events. One of the most abundant is a species composed of the ␣7 gene product and having a relative calcium permeability equivalent to that of NMDA receptors. The ␣7-containing receptors can be found presynaptically where they modulate transmitter release, and postsynaptically where they generate excitatory responses. They can also be found in perisynaptic locations where they modulate other inputs to the neuron and can activate a variety of downstream signaling pathways. The effects the receptors produce depend critically on the sites at which they are clustered. Instructive preparations for examining ␣7-containing receptors are the rat hippocampus, where they are thought to play a modulatory role, and the chick ciliary ganglion, where they participate in throughput transmission as well as regulatory signaling. Relatively high levels of ␣7-containing receptors are found in the two preparations, and the receptors display a variety of synaptic options and functions in the two cases. Progress is starting to be made in understanding the mechanisms responsible for localizing the receptors at specific sites and in identifying components tethered in the vicinity of the receptors that may facilitate signal transduction and downstream signaling.

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“…One class of neuronal nAChRs is a pentamer that has the general composition of two ␣ (ligand-binding) and three ␤ subunits (Anand et al, 1991;Cooper et al, 1991). The second class of neuronal nAChRs is distinguished pharmacologically by sensitivity to ␣-bungarotoxin (␣-bgt), is composed of distinct ␣-type subunits, and functions largely as homopentamers (Vernallis et al, 1993;Chen and Patrick, 1997;Drisdel and Green, 2000). There is great interest in defining, within one neuron population, the diversity of nAChR subtypes that are expressed and their subunit composition.…”

Section: Diversity Of Nachr Subtypesmentioning

confidence: 99%

“…The ␣3-nAChRs, composed of ␣3, ␣5, and ␤4 (occasionally ␤2) subunits, are largely concentrated in the postsynaptic membrane (Jacob et al, 1986;Loring and Zigmond, 1987;Vernallis et al, 1993;Horch and Sargent, 1995). In contrast, the ␣7-nAChRs, composed of ␣7 subunits, are excluded from the synapse and restricted to perisynaptic regions on somatic spines (Jacob and Berg, 1983;Loring et al, 1985;Vernallis et al, 1993;Horch and Sargent, 1995;Shoop et al, 1999;Conroy and Berg, 2000). The ␣3-nAChRs mediate fast excitatory synaptic transmission through the ganglion at all developmental stages, while the ␣7-nAChRs contribute to fast throughput signaling, but only at early embryonic ages (Chang and Berg 1999).…”

Section: Inductive Effects Of Innervation On Nachr Expressionmentioning

confidence: 99%

Regulatory mechanisms that govern nicotinic synapse formation in neurons

et al. 2002

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Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

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Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes

Cited by 293 publications

References 37 publications

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

Regulatory mechanisms that govern nicotinic synapse formation in neurons

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