ArticleThe Journal of biological chemistry2014
Calcium regulates molecular interactions of otoferlin with soluble NSF attachment protein receptor (SNARE) proteins required for hair cell exocytosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Changing subplate circuits: Early activity dependent circuit plasticity.Frontiers in cellular neuroscience · 2022Pooled it
- Expression of nestin, parvalbumin and otoferlin during cochlear development in the mouse: an immunofluorescence study.European journal of histochemistry : EJH · 2025Article
- Toxoplasma FER1 is a versatile and dynamic mediator of differential microneme trafficking and microneme exocytosis.Scientific reports · 2024Article
- Analysis of Dysferlin Direct Interactions with Putative Repair Proteins Links Apoptotic Signaling to CaInternational journal of molecular sciences · 2023Article
- Otoferlin as a multirole CaFrontiers in cellular neuroscience · 2023Review
- Impaired Hearing and Altered Subplate Circuits During the First and Second Postnatal Weeks of Otoferlin-Deficient Mice.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred.BMC medical genomics · 2021Article
- Whole-Exome Sequencing Reveals a Rare Variant ofFrontiers in genetics · 2021Article
- Otoferlin C2F Domain-Induced Changes in Membrane Structure Observed by Sum Frequency Generation.Biophysical journal · 2019Article
- Review
- Viral Transfer of Mini-Otoferlins Partially Restores the Fast Component of Exocytosis and Uncovers Ultrafast Endocytosis in Auditory Hair Cells of Otoferlin Knock-Out Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- GABA is a modulator, rather than a classical transmitter, in the medial nucleus of the trapezoid body-lateral superior olive sound localization circuit.The Journal of physiology · 2019Article
- Fer1l6 is essential for the development of vertebrate muscle tissue in zebrafish.Molecular biology of the cell · 2019Article
- Emerging Functional Differences between the Synaptotagmin and Ferlin Calcium Sensor Families.Biochemistry · 2017Article
- Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing.The Journal of comparative neurology · 2017Article
- Dopamine D1A directly interacts with otoferlin synaptic pathway proteins: Ca2+ and phosphorylation underlie an NSF-to-AP2mu1 molecular switch.The Biochemical journal · 2017Article
- Activity-Dependent Phosphorylation by CaMKIIδ Alters the CaFrontiers in synaptic neuroscience · 2017Article
- A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy.Saudi medical journal · 2016Article
- Article
- Relating structure and function of inner hair cell ribbon synapses.Cell and tissue research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in otoferlin, a C2 domain-containing ferlin family protein, cause non-syndromic hearing loss in humans (DFNB9 deafness). Furthermore, transmitter secretion of cochlear inner hair cells is compromised in mice lacking otoferlin. In the present study, we show that the C2F domain of otoferlin directly binds calcium (KD = 267 μM) with diminished binding in a pachanga (D1767G) C2F mouse mutation. Calcium was found to differentially regulate binding of otoferlin C2 domains to target SNARE (t-SNARE) proteins and phospholipids. C2D-F domains interact with the syntaxin-1 t-SNARE motif with maximum binding within the range of 20-50 μM Ca(2+). At 20 μM Ca(2+), the dissociation rate was substantially lower, indicating increased binding (KD = ∼10(-9)) compared with 0 μM Ca(2+) (KD = ∼10(-8)), suggesting a calcium-mediated stabilization of the C2 domain·t-SNARE complex. C2A and C2B interactions with t-SNAREs were insensitive to calcium. The C2F domain directly binds the t-SNARE SNAP-25 maximally at 100 μM and with reduction at 0 μM Ca(2+), a pattern repeated for C2F domain interactions with phosphatidylinositol 4,5-bisphosphate. In contrast, C2F did not bind the vesicle SNARE protein synaptobrevin-1 (VAMP-1). Moreover, an antibody targeting otoferlin immunoprecipitated syntaxin-1 and SNAP-25 but not synaptobrevin-1. As opposed to an increase in binding with increased calcium, interactions between otoferlin C2F domain and intramolecular C2 domains occurred in the absence of calcium, consistent with intra-C2 domain interactions forming a "closed" tertiary structure at low calcium that "opens" as calcium increases. These results suggest a direct role for otoferlin in exocytosis and modulation of calcium-dependent membrane fusion.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.