ArticleThe Journal of biological chemistry2011
Transit defect of potassium-chloride Co-transporter 3 is a major pathogenic mechanism in hereditary motor and sensory neuropathy with agenesis of the corpus callosum.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 30 citations in OpenAlex.
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- Neuron cilia restrain glial KCC-3 to a microdomain to regulate multisensory processing.Cell reports · 2024Article
- Neuron cilia constrain glial regulators to microdomains around distal neurons.bioRxiv : the preprint server for biology · 2023Article
- Expanding the phenotype ofBMJ case reports · 2021Article
- Structures and an activation mechanism of human potassium-chloride cotransporters.Science advances · 2020Article
- The genetic landscape of the human solute carrier (SLC) transporter superfamily.Human genetics · 2019Article
- Underdominant KCC3b R31I association with blood sodium concentration in domestic sheep suggests role in oligomer function.Animal genetics · 2017Article
- Article
- K-Cl cotransporters, cell volume homeostasis, and neurological disease.Trends in molecular medicine · 2015Review
- Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.American journal of physiology. Renal physiology · 2013Article
- N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swelling.The Journal of biological chemistry · 2013Article
- A trafficking-deficient mutant of KCC3 reveals dominant-negative effects on K-Cl cotransport function.PloS one · 2013Article
- Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics.PloS one · 2013Article
- WNK1/HSN2 mutation in human peripheral neuropathy deregulates KCC2 expression and posterior lateral line development in zebrafish (Danio rerio).PLoS genetics · 2013Article
- The biogenesis of potassium transporters: implications of disease-associated mutations.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Missense and protein-truncating mutations of the human potassium-chloride co-transporter 3 gene (KCC3) cause hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), which is a severe neurodegenerative disease characterized by axonal dysfunction and neurodevelopmental defects. We previously reported that KCC3-truncating mutations disrupt brain-type creatine kinase-dependent activation of the co-transporter through the loss of its last 140 amino acids. Here, we report a novel and more distal HMSN/ACC-truncating mutation (3402C → T; R1134X) that eliminates only the last 17 residues of the protein. This small truncation disrupts the interaction with brain-type creatine kinase in mammalian cells but also affects plasma membrane localization of the mutant transporter. Although it is not truncated, the previously reported HMSN/ACC-causing 619C → T (R207C) missense mutation also leads to KCC3 loss of function in Xenopus oocyte flux assay. Immunodetection in Xenopus oocytes and in mammalian cultured cells revealed a decreased amount of R207C at the plasma membrane, with significant retention of the mutant proteins in the endoplasmic reticulum. In mammalian cells, curcumin partially corrected these mutant protein mislocalizations, with more protein reaching the plasma membrane. These findings suggest that mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations.
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.