title: Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor.
abstract: We report that anoctamin 1 (ANO1; also known as TMEM16A) Ca(2+)-activated Cl(-) channels in small neurons from dorsal root ganglia are preferentially activated by particular pools of intracellular Ca(2+). These ANO1 channels can be selectively activated by the G protein-coupled receptor (GPCR)-induced release of Ca(2+) from intracellular stores but not by Ca(2+) influx through voltage-gated Ca(2+) channels. This ability to discriminate between Ca(2+) pools was achieved by the tethering of ANO1-containing plasma membrane domains, which also contained GPCRs such as bradykinin receptor 2 and protease-activated receptor 2, to juxtamembrane regions of the endoplasmic reticulum. Interaction of the carboxyl terminus and the first intracellular loop of ANO1 with IP3R1 (inositol 1,4,5-trisphosphate receptor 1) contributed to the tethering. Disruption of membrane microdomains blocked the ANO1 and IP3R1 interaction and resulted in the loss of coupling between GPCR signaling and ANO1. The junctional signaling complex enabled ANO1-mediated excitation in response to specific Ca(2+)signals rather than to global changes in intracellular Ca(2+).
authors: Faculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors: Xin
authors: X
authors: Jin
authors: Shihab
authors: S
authors: Shah
authors: Yani
authors: Y
authors: Liu
authors: Huiran
authors: H
authors: Zhang
authors: Meredith
authors: M
authors: Lees
authors: Zhaojun
authors: Z
authors: Fu
authors: Jonathan D
authors: JD
authors: Lippiat
authors: David J
authors: DJ
authors: Beech
authors: Asipu
authors: A
authors: Sivaprasadarao
authors: Stephen A
authors: SA
authors: Baldwin
authors: Hailin
authors: H
authors: Zhang
authors: Nikita
authors: N
authors: Gamper
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C552942:ANO1 protein, rat; D000075369:Anoctamin-1; D018118:Chloride Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D043782:Receptor, Bradykinin B2; D044464:Receptor, PAR-2; D043562:Receptors, G-Protein-Coupled; D002118:Calcium
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