ArticleThe Journal of biological chemistry2015
Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Abnormal ClC-3/TMEM9-mediated endosomal ion transport in CLCN3-associated neurodevelopmental disease.EMBO molecular medicine · 2026Article
- CFTR and ClC-3 Transport Fluoride Differently and Cause Dental Fluorosis in Different Ways.Biomolecules · 2026Article
- Endosomal 2Cl-/H+ exchangers regulate neuronal excitability by tuning Kv7/KCNQ channel density.Brain : a journal of neurology · 2025Article
- Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)PNature structural & molecular biology · 2025Article
- Disruption of ClC-3-mediated 2ClScientific reports · 2025Article
- Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain.Genome biology · 2025Article
- Article
- Molecular requirements of chromogranin B for the long-sought anion shunter of regulated secretion.International journal of biological macromolecules · 2025Article
- Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity.Nature communications · 2025Article
- Chloride channel-3 regulates sodium-iodide symporter expression and localization in the thyroids of mice on a high-iodide diet.Frontiers in nutrition · 2025Article
- TMEM9B Regulates Endosomal ClC-3 and ClC-4 Transporters.Life (Basel, Switzerland) · 2024Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.Journal of neurology · 2024Article
- Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.Human genetics · 2024Article
- Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1.Brain : a journal of neurology · 2023Article
- Biophysical Aspects of Neurodegenerative and Neurodevelopmental Disorders Involving Endo-/Lysosomal CLC ClLife (Basel, Switzerland) · 2023Review
- Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.The Journal of membrane biology · 2023Article
- Chloride Channel Family in the EuhalophyteInternational journal of molecular sciences · 2023Article
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ClC-3 is a member of the CLC family of anion channels and transporters, for which multiple functional properties and subcellular localizations have been reported. Since alternative splicing often results in proteins with diverse properties, we investigated to what extent alternative splicing might influence subcellular targeting and function of ClC-3. We identified three alternatively spliced ClC-3 isoforms, ClC-3a, ClC-3b, and ClC-3c, in mouse brain, with ClC-3c being the predominant splice variant. Whereas ClC-3a and ClC-3b are present in late endosomes/lysosomes, ClC-3c is targeted to recycling endosomes via a novel N-terminal isoleucine-proline (IP) motif. Surface membrane insertion of a fraction of ClC-3c transporters permitted electrophysiological characterization of this splice variant through whole-cell patch clamping on transfected mammalian cells. In contrast, neutralization of the N-terminal dileucine-like motifs was required for functional analysis of ClC-3a and ClC-3b. Heterologous expression of ClC-3a or ClC-3b carrying mutations in N-terminal dileucine motifs as well as WTClC-3c in HEK293T cells resulted in outwardly rectifying Cl(-) currents with significant capacitive current components. We conclude that alternative splicing of Clcn3 results in proteins with different subcellular localizations, but leaves the transport function of the proteins unaffected.
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