The alpha1 subunit of nicotinic acetylcholine receptors in the inner ear: transcriptional regulation by ATOH1 and co-expression with the gamma subunit in hair cells

SCHEFFER D; SAGE C; PLAZAS PV; MINGQIAN H; WEDEMEYER C; ZHANG D; CHEN Z; ELGOYHEN AB; COREY DP; PINGAULT V

J Neurochemistry

Año: 2007 vol. 103 p. 2651 - 2664

Abstract Acetylcholine is a key neurotransmitter of the inner ear efferent system. In this study, we identify two novel nAChR subunits in the inner ear: a1 and c, encoded by Chrna1 anda1 and c, encoded by Chrna1 and Chrng, respectively. In situ hybridization shows that the messages of these two subunits are present in vestibular and cochlear hair cells during early development. Chrna1 and messages of these two subunits are present in vestibular and cochlear hair cells during early development. Chrna1 and , respectively. In situ hybridization shows that the messages of these two subunits are present in vestibular and cochlear hair cells during early development. Chrna1 andChrna1 and Chrng expression begin at embryonic stage E13.5 in the vestibular system and E17.5 in the organ of Corti. Chrna1 vestibular system and E17.5 in the organ of Corti. Chrna1 expression begin at embryonic stage E13.5 in the vestibular system and E17.5 in the organ of Corti. Chrna1Chrna1 message continues through P7, whereas Chrng is undetectable at post-natal stage P6. The a1 and c subunits are known as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. at post-natal stage P6. The a1 and c subunits are known as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. Chrng is undetectable at post-natal stage P6. The a1 and c subunits are known as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation. a1 and c subunits are known as muscle-type nAChR subunits and are surprisingly expressed in hair cells which are sensory-neural cells. We also show that ATOH1/MATH1, a transcription factor essential for hair cell development, directly activates CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1 transcription. Electrophoretic mobility-shift assays and supershift assays showed that ATOH1/E47 heterodimers selectively bind on two E boxes located in the proximal promoter of CHRNA1. Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in Xenopus of ATOH1 in the inner ear. Co-expression in Xenopus . Thus, Chrna1 could be the first transcriptional target of ATOH1 in the inner ear. Co-expression in XenopusXenopus oocytes of the a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a1 subunit does not change the electrophysiological properties of the a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition to cells transiently express a1c-containing nAChRs in addition to a9a10 receptor. We suggest that hair cells transiently express a1c-containing nAChRs in addition toa1c-containing nAChRs in addition to a9a10, and that these may have a role during development of the inner ear innervation. the inner ear innervation. 9a10, and that these may have a role during development of the inner ear innervation.