ArticleMolecular biology of the cell2008
Exon loss accounts for differential sorting of Na-K-Cl cotransporters in polarized epithelial cells.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 86 citations in OpenAlex.
- Chasing the ghost in the code: highlighting the mystery of a rare genetic condition.American journal of physiology. Cell physiology · 2026Review
- Complete omission of exon 21 from Slc12a2 transcripts in mice results in hearing loss.Scientific reports · 2025Article
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- NKCC1 and KCC2 Chloride Transporters Have Different Membrane Dynamics on the Surface of Hippocampal Neurons.Cells · 2023Article
- Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Article
- Confluence and tight junction dependence of volume regulation in epithelial tissue.Molecular biology of the cell · 2022Article
- Intestinal secretory mechanisms and diarrhea.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Self-organization of apical membrane protein sorting in epithelial cells.The FEBS journal · 2022Article
- Role of Nuclear Lamin A/C in the Regulation of Nav1.5 Channel and Microtubules: Lesson From the Pathogenic Lamin A/C Variant Q517X.Frontiers in cell and developmental biology · 2022Article
- NKCC1: Newly Found as a Human Disease-Causing Ion Transporter.Function (Oxford, England) · 2021Review
- NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data.Cells · 2020Review
- Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans.PLoS genetics · 2020Article
- Molecular regulation of NKCC2 in blood pressure control and hypertension.Current opinion in nephrology and hypertension · 2019Review
- Genetic and pharmacological inactivation of apical NaAmerican journal of physiology. Cell physiology · 2019Article
- A dileucine motif in the COOH-terminal domain of NKCC1 targets the cotransporter to the plasma membrane.American journal of physiology. Cell physiology · 2019Article
- Role of Alström syndrome 1 in the regulation of blood pressure and renal function.JCI insight · 2018Article
- Mistargeting of a truncated Na-K-2Cl cotransporter in epithelial cells.American journal of physiology. Cell physiology · 2018Article
- Azosemide is more potent than bumetanide and various other loop diuretics to inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and hNKCC1B.Scientific reports · 2018Article
- Directional Fluid Transport across Organ-Blood Barriers: Physiology and Cell Biology.Cold Spring Harbor perspectives in biology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The renal Na-K-Cl cotransporter (NKCC2) is selectively expressed in the apical membranes of cells of the mammalian kidney, where it is the target of the clinically important loop diuretics. In contrast, the "secretory" NKCC1 cotransporter is localized in the basolateral membranes of many epithelia. To identify the sorting signal(s) that direct trafficking of NKCCs, we generated chimeras between the two isoforms and expressed these constructs in polarized renal epithelial cell lines. This analysis revealed an amino acid stretch in NKCC2 containing apical sorting information. The NKCC1 C terminus contains a dileucine motif that constitutes the smallest essential component of its basolateral sorting signal. NKCC1 lacking this motif behaves as an apical protein. Examination of the NKCC gene structure reveals that this dileucine motif is encoded by an additional exon in NKCC1 absent in NKCC2. Phylogenetic analysis of this exon suggests that the evolutionary loss of this exon from the gene encoding the basolateral NKCC1 constitutes a novel mechanism that accounts for the apical sorting of the protein encoded by the NKCC2 gene.
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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.