ArticleProceedings of the National Academy of Sciences of the United States of America2014
Preassociated apocalmodulin mediates Ca2+-dependent sensitization of activation and inactivation of TMEM16A/16B Ca2+-gated Cl- channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Research and optimization of screening strategy for calcium-activated chloride channel modulators guided by electrophysiological characteristics.Scientific reports · 2026Article
- From BEST1 mutations to retinal regeneration: integrating stem cell-derived RPE models and gene correction strategies.Frontiers in cell and developmental biology · 2026Review
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- Calmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells.Membranes · 2021Article
- Article
- CaMolecules and cells · 2021Article
- Article
- Calcium-Activated Chloride Channels in Myometrial and Vascular Smooth Muscle.Frontiers in physiology · 2021Review
- Transduction and Adaptation Mechanisms in the Cilium or Microvilli of Photoreceptors and Olfactory Receptors From Insects to Humans.Frontiers in cellular neuroscience · 2021Review
- The cyclic AMP signaling pathway in the rodent main olfactory system.Cell and tissue research · 2021Review
- Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Designer genetically encoded voltage-dependent calcium channel inhibitors inspired by RGK GTPases.The Journal of physiology · 2020Review
- Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations.Scientific reports · 2019Article
- Molecular basis of PIPNature communications · 2019Article
- Dual CaCommunications biology · 2019Article
- Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium Cells: A Disease-in-a-dish Model for BEST1 Mutations.Journal of visualized experiments : JoVE · 2018Article
- ATP activates bestrophin ion channels through direct interaction.Nature communications · 2018Article
- Expression and Purification of Mammalian Bestrophin Ion Channels.Journal of visualized experiments : JoVE · 2018Article
- CaInternational journal of molecular sciences · 2018Review
- Resident Calmodulin Primes NMDA Receptors for CaBiophysical journal · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ca(2+)-activated chloride currents carried via transmembrane proteins TMEM16A and TMEM16B regulate diverse processes including mucus secretion, neuronal excitability, smooth muscle contraction, olfactory signal transduction, and cell proliferation. Understanding how TMEM16A/16B are regulated by Ca(2+) is critical for defining their (patho)/physiological roles and for rationally targeting them therapeutically. Here, using a bioengineering approach--channel inactivation induced by membrane-tethering of an associated protein (ChIMP)--we discovered that Ca(2+)-free calmodulin (apoCaM) is preassociated with TMEM16A/16B channel complexes. The resident apoCaM mediates two distinct Ca(2+)-dependent effects on TMEM16A, as revealed by expression of dominant-negative CaM1234. These effects are Ca(2+)-dependent sensitization of activation (CDSA) and Ca(2+)-dependent inactivation (CDI). CDI and CDSA are independently mediated by the N and C lobes of CaM, respectively. TMEM16A alternative splicing provides a mechanism for tuning apoCaM effects. Channels lacking splice segment b selectively lost CDI, and segment a is necessary for apoCaM preassociation with TMEM16A. The results reveal multidimensional regulation of TMEM16A/16B by preassociated apoCaM and introduce ChIMP as a versatile tool to probe the macromolecular complex and function of Ca(2+)-activated chloride channels.
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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.