α-Bungarotoxin Receptors Contain α7 Subunits in Two Different Disulfide-Bonded Conformations

Rakhilin, Sergey; Drisdel, Renaldo C.; Sagher, Daphna; McGehee, Daniel S.; Vallejo, Yolanda; Green, William N.

doi:10.1083/jcb.146.1.203

Cited by 45 publications

(55 citation statements)

References 63 publications

(22 reference statements)

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“…4). In other heterologous expression systems based on transfected cell lines, the situation is even worse, as no functional receptors are detected at the cell membrane (32)(33)(34). However, the presence of hRIC-3 facilitates the transport of ␣7 nAChRs so that 41% of total mature receptors reach the cell membrane.…”

Section: Discussionmentioning

confidence: 93%

Dual Role of the RIC-3 Protein in Trafficking of Serotonin and Nicotinic Acetylcholine Receptors

Castillo

Mulet

Gutiérrez

et al. 2005

Journal of Biological Chemistry

176

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The ric-3 gene is required for maturation of nicotinic acetylcholine receptors in Caenorhabditis elegans. The human homolog of RIC-3, hRIC-3, enhances expression of ␣7 nicotinic receptors in Xenopus laevis oocytes, whereas it totally abolishes expression of ␣4␤2 nicotinic and 5-HT 3 serotonergic receptors. Both the N-terminal region of hRIC-3, which contains two transmembrane segments, and the C-terminal region are needed for these differential effects. hRIC-3 inhibits receptor expression by hindering export of mature receptors to the cell membrane. By using chimeric proteins made of ␣7 and 5-HT 3 receptors, we have shown that the presence of an extracellular isoleucine close to the first transmembrane receptor fragment is responsible for the transport arrest induced by hRIC-3. Enhancement of ␣7 receptor expression occurs, at least, at two levels: by increasing the number of mature receptors and facilitating its transport to the membrane. Certain amino acids of a putative amphipathic helix present at the large cytoplasmic region of the ␣7 subunit are required for these actions. Therefore, hRIC-3 can act as a specific regulator of receptor expression at different levels.

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Section: Discussionmentioning

confidence: 93%

Dual Role of the RIC-3 Protein in Trafficking of Serotonin and Nicotinic Acetylcholine Receptors

Castillo

Mulet

Gutiérrez

et al. 2005

Journal of Biological Chemistry

176

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“…Given that T cells express ␣7-nAChR subunits essentially identical to the neuronal receptor, failure to detect a functional Ca 2ϩ -permeating channel is surprising. However, even in some PC12 cells and TsA201 cells transfected with ␣7-nAChR cDNA, the presence of full-length ␣7-nAChR mRNA transcripts and membrane-localized ␣7-nAChRs was not sufficient to generate a functional nicotine-sensitive ligand-gated Ca 2ϩ response (31,34). RIC-3, a chaperon protein, has recently been implicated in the functional association of ␣7-nAChRs (54).…”

Section: Discussionmentioning

confidence: 99%

“…TsA201 cells transfected with ␣7-nAChR cDNA express ␣7-nAChRs on the cell surface, but do not produce nicotine-induced inward currents (34). Moreover, in mammalian cells ␣7-nAChRs might require additional proteins to form a functional cationic channel (35,36).…”

Section: T He Nicotinic Acetylcholine Receptors (Nachrs)mentioning

confidence: 99%

T Cells Express α7-Nicotinic Acetylcholine Receptor Subunits That Require a Functional TCR and Leukocyte-Specific Protein Tyrosine Kinase for Nicotine-Induced Ca2+ Response

Razani‐Boroujerdi

Boyd

Dávila‐García

et al. 2007

The Journal of Immunology

157

132

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Acute and chronic effects of nicotine on the immune system are usually opposite; acute treatment stimulates while chronic nicotine suppresses immune and inflammatory responses. Nicotine acutely raises intracellular calcium ([Ca2+]i) in T cells, but the mechanism of this response is unclear. Nicotinic acetylcholine receptors (nAChRs) are present on neuronal and non-neuronal cells, but while in neurons, nAChRs are cation channels that participate in neurotransmission; their structure and function in nonexcitable cells are not well-defined. In this communication, we present evidence that T cells express α7-nAChRs that are critical in increasing [Ca2+]i in response to nicotine. Cloning and sequencing of the receptor from human T cells showed a full-length transcript essentially identical to the neuronal α7-nAChR subunit (>99.6% homology). These receptors are up-regulated and tyrosine phosphorylated by treatment with nicotine, anti-TCR Abs, or Con A. Furthermore, knockdown of the α7-nAChR subunit mRNA by RNA interference reduced the nicotine-induced Ca2+ response, but unlike the neuronal receptor, α-bungarotoxin and methyllycaconitine not only failed to block, but also actually raised [Ca2+]i in T cells. The nicotine-induced release of Ca2+ from intracellular stores in T cells did not require extracellular Ca2+, but, similar to the TCR-mediated Ca2+ response, required activation of protein tyrosine kinases, a functional TCR/CD3 complex, and leukocyte-specific tyrosine kinase. Moreover, CD3ζ and α7-nAChR coimmunoprecipitated with anti-CD3ζ or anti-α7-nAChR Abs. These results suggest that in T cells, α7-nAChR, despite its close sequence homology with neuronal α7-nAChR, fails to form a ligand-gated Ca2+ channel, and that the nicotine-induced rise in [Ca2+]i in T cells requires functional TCR/CD3 and leukocyte-specific tyrosine kinase.

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“…conformations within homomeric nicotinic ␣7 receptors, see Rakhilin et al (1999)]. The lack of crystal structures for homooligomeric proteins with no ligand bound means that the evidence on this point is limited.…”

Section: Are the Sites Different Before Agonist Binds?mentioning

confidence: 99%

The Activation Mechanism of α1 Homomeric Glycine Receptors

Beato

Groot-Kormelink²,

Colquhoun³

et al. 2004

J. Neurosci.

103

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The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant ␣1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10 -1000 M). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open-shut correlation, and single-channel P open dose-response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer.

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α-Bungarotoxin Receptors Contain α7 Subunits in Two Different Disulfide-Bonded Conformations

Cited by 45 publications

References 63 publications

Dual Role of the RIC-3 Protein in Trafficking of Serotonin and Nicotinic Acetylcholine Receptors

Dual Role of the RIC-3 Protein in Trafficking of Serotonin and Nicotinic Acetylcholine Receptors

T Cells Express α7-Nicotinic Acetylcholine Receptor Subunits That Require a Functional TCR and Leukocyte-Specific Protein Tyrosine Kinase for Nicotine-Induced Ca2+ Response

The Activation Mechanism of α1 Homomeric Glycine Receptors

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