Epitope mapping of polyclonal and monoclonal antibodies against two α-bungarotoxin-binding α subunits from neuronal nicotinic receptors

McLane, Kathryn E.; Wu, Xiadong; Lindstrom, Jon; Conti‐Tronconi, Bianca M.

doi:10.1016/0165-5728(92)90096-4

Cited by 42 publications

(23 citation statements)

References 34 publications

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“…Epitope mapping has shown that mAb306 recognizes the sequence corresponding to the cytoplasmic loop residues 380–400 of the α7nAChR from rat and chicken (Schoepfer et al, 1990; McLane et al, 1992). This antibody was used previously to study the α7nAChR distribution, in (1) rat and mouse brain using bright field (Dominguez del Toro et al, 1994; Duffy et al, 2009) or electron microscopy (Fabian-Fine et al, 2001; Levy and Aoki, 2002; Duffy et al, 2009) and (2) macaque brain using fluorescent microscopy (Centeno et al, 2006).…”

Section: Methodsmentioning

confidence: 99%

Dopamine D2 and acetylcholine α7 nicotinic receptors have subcellular distributions favoring mediation of convergent signaling in the mouse ventral tegmental area

et al. 2013

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Alpha7 nicotinic acetylcholine receptors (α7nAChRs) mediate nicotine-induced burst-firing of dopamine neurons in the ventral tegmental area (VTA), a limbic brain region critically involved in reward and in dopamine D2 receptor (D2R)-related cortical dysfunctions associated with psychosis. The known presence of α7nAChRs and Gi-coupled D2Rs in dopamine neurons of the VTA suggests that these receptors are targeted to at least some of the same neurons in this brain region. To test this hypothesis, we used electron microscopic immunolabeling of antisera against peptide sequences of α7nACh and D2 receptors in the mouse VTA. Dual D2R and α7nAChR labeling was seen in many of the same somata (co-localization over 97%) and dendrites (co-localization over 49%), where immunoreactivity for each of the receptors was localized to endomembranes as well as to non-synaptic or synaptic plasma membranes often near excitatory-type synapses. In comparison with somata and dendrites, many more small axons and axon terminals were separately labeled for each of the receptors. Thus, single-labeled axon terminals were predominant for both α7nAChR (57.9%) and D2R (89.0%). The majority of the immunolabeled axonal profiles contained D2R-immunoreactivity (81.6%) and formed either symmetric or asymmetric synapses consistent with involvement in the release of both inhibitory and excitatory transmitters. Of 160 D2R-labeled terminals, 81.2% were presynaptic to dendrites that expressed α7nAChR alone or together with the D2R. Numerous glial processes inclusive of those enveloping either excitatory- or inhibitory-type synapses also contained single labeling for D2R (n = 152) and α7nAChR (n =561). These results suggest that classic antipsychotic drugs, all of which block the D2R, may facilitate α7nAChR-mediated burst-firing by elimination of D2R-dependent inhibition in neurons expressing both receptors as well as by indirect pre-synaptic and glial mechanisms.

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Section: Methodsmentioning

confidence: 99%

Dopamine D2 and acetylcholine α7 nicotinic receptors have subcellular distributions favoring mediation of convergent signaling in the mouse ventral tegmental area

et al. 2013

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“…Properties of mAbs to the MIR used are summarized in Table 1. mAb 306 and mAb 319 are directed at the cytoplasmic domain of α7 (McLane et al, 1992). …”

Section: Methodsmentioning

confidence: 99%

Main Immunogenic Region Structure Promotes Binding of Conformation-Dependent Myasthenia Gravis Autoantibodies, Nicotinic Acetylcholine Receptor Conformation Maturation, and Agonist Sensitivity

Luo¹,

Taylor²,

Losen³

et al. 2009

J. Neurosci.

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The main immunogenic region (MIR) is a conformation-dependent region at the extracellular apex of ␣1 subunits of muscle nicotinic acetylcholine receptor (AChR) that is the target of half or more of the autoantibodies to muscle AChRs in human myasthenia gravis and rat experimental autoimmune myasthenia gravis. By making chimeras of human ␣1 subunits with ␣7 subunits, both MIR epitopes recognized by rat mAbs and by the patient-derived human mAb 637 to the MIR were determined to consist of two discontiguous sequences, which are adjacent only in the native conformation. The MIR, including loop ␣1 67-76 in combination with the N-terminal ␣ helix ␣1 1-14, conferred high-affinity binding for most rat mAbs to the MIR. However, an additional sequence corresponding to ␣1 15-32 was required for high-affinity binding of human mAb 637. A water soluble chimera of Aplysia acetylcholine binding protein with the same ␣1 MIR sequences substituted was recognized by a majority of human, feline, and canine myasthenia gravis sera. The presence of the ␣1 MIR sequences in ␣1/␣7 chimeras greatly promoted AChR expression and significantly altered the sensitivity to activation. This reveals a structural and functional, as well as antigenic, significance of the MIR.

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“…[25][26][27]; for mAb 306, see Refs. [28][29][30]). The a7 antibody specifically binds to a sequence in the cytoplasmic loop [30] and will not therefore cross react with the recently described acetylcholine binding protein which shares homology with extracellular portion of the a7 nAChR subunit [31].…”

Section: Immunohistochemistrymentioning

confidence: 97%

Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology

Teaktong

Graham

Court

et al. 2004

Journal of the Neurological Sciences

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Epitope mapping of polyclonal and monoclonal antibodies against two α-bungarotoxin-binding α subunits from neuronal nicotinic receptors

Cited by 42 publications

References 34 publications

Dopamine D2 and acetylcholine α7 nicotinic receptors have subcellular distributions favoring mediation of convergent signaling in the mouse ventral tegmental area

Dopamine D2 and acetylcholine α7 nicotinic receptors have subcellular distributions favoring mediation of convergent signaling in the mouse ventral tegmental area

Main Immunogenic Region Structure Promotes Binding of Conformation-Dependent Myasthenia Gravis Autoantibodies, Nicotinic Acetylcholine Receptor Conformation Maturation, and Agonist Sensitivity

Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology

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