ArticleThe Journal of physiology2013
Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy.Human molecular genetics · 2023Article
- Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes.EMBO molecular medicine · 2022Article
- Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction.Nucleic acids research · 2020Article
- Hair Cell Afferent Synapses: Function and Dysfunction.Cold Spring Harbor perspectives in medicine · 2019Review
- Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Single-Channel Resolution of the Interaction between C-Terminal CaBiophysical journal · 2019Article
- Voltage-Gated Calcium Channels: Key Players in Sensory Coding in the Retina and the Inner Ear.Physiological reviews · 2018Review
- Role of a conserved glutamine in the function of voltage-gated CaThe Journal of biological chemistry · 2018Article
- Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome.The Journal of clinical investigation · 2018Article
- Inframe deletion of humanJournal of medical genetics · 2018Article
- Emerging Gene Therapies for Genetic Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2017Review
- Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.Nature biotechnology · 2017Article
- CaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- New insights into cochlear sound encoding.F1000Research · 2016Review
- Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities.Biochimica et biophysica acta · 2015Review
- Regulation of Postsynaptic Stability by the L-type Calcium Channel CaV1.3 and its Interaction with PDZ Proteins.Current molecular pharmacology · 2015Review
- Voltage-Gated Cav1 Channels in Disorders of Vision and Hearing.Current molecular pharmacology · 2015Review
- Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly.The Journal of cell biology · 2014Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Cav1.3 channels mediate Ca(2+) influx that triggers exocytosis of glutamate at cochlear inner hair cell (IHC) synapses. Harmonin is a PDZ-domain-containing protein that interacts with the C-terminus of the Cav1.3 α1 subunit (α11.3) and controls cell surface Cav1.3 levels by promoting ubiquitin-dependent proteosomal degradation. However, PDZ-domain-containing proteins have diverse functions and regulate other Cav1.3 properties, which could collectively influence presynaptic transmitter release. Here, we report that harmonin binding to the α11.3 distal C-terminus (dCT) enhances voltage-dependent facilitation (VDF) of Cav1.3 currents both in transfected HEK293T cells and in mouse inner hair cells. In HEK293T cells, this effect of harmonin was greater for Cav1.3 channels containing the auxiliary Cav β1 than with the β2 auxiliary subunit. Cav1.3 channels lacking the α11.3 dCT were insensitive to harmonin modulation. Moreover, the 'deaf-circler' dfcr mutant form of harmonin, which does not interact with the α11.3 dCT, did not promote VDF. In mature IHCs from mice expressing the dfcr harmonin mutant, Cav1.3 VDF was less than in control IHCs. This difference was not observed between control and dfcr IHCs prior to hearing onset. Membrane capacitance recordings from dfcr IHCs revealed a role for harmonin in synchronous exocytosis and in increasing the efficiency of Ca(2+) influx for triggering exocytosis. Collectively, our results indicate a multifaceted presynaptic role of harmonin in IHCs in regulating Cav1.3 Ca(2+) channels and exocytosis.
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