ArticleMolecular biology of the cell2010
The Na+/H+ exchanger NHE6 in the endosomal recycling system is involved in the development of apical bile canalicular surface domains in HepG2 cells.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
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- Missense variants in SLC9A6 cause partial epilepsy without neurodevelopmental delay.Orphanet journal of rare diseases · 2025Article
- Dexamethasone disrupts intracellular pH homeostasis to delay coronavirus infectious bronchitis virus cell entry via sodium hydrogen exchanger 3 activation.Journal of virology · 2025Article
- Robust inhibitory glycinergic transmission and the effect of bafilomycin, folimycin and EIPA: lessons from the auditory brainstem.Frontiers in cellular neuroscience · 2025Article
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Slc9a6 mutation causes Purkinje cell loss and ataxia in the shaker rat.Human molecular genetics · 2023Article
- Altered distribution and localization of organellar NaTranslational psychiatry · 2023Article
- The Physiological Function and Potential Role of the Ubiquitous NaInternational journal of molecular sciences · 2022Review
- Donor Splice Site Variant inMedicina (Kaunas, Lithuania) · 2022Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Loss of Christianson Syndrome NaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load.eLife · 2021Article
- Protons to Patients: targeting endosomal NaThe FEBS journal · 2021Review
- Might proton pump or sodium-hydrogen exchanger inhibitors be of value to ameliorate SARs-CoV-2 pathophysiology?Physiological reports · 2021Review
- Quantitative Imaging of BiochemistryACS central science · 2020Review
- A Molecular Mechanism Underlying Genotype-Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations.Hepatology (Baltimore, Md.) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polarized epithelial cells develop and maintain distinct apical and basolateral surface domains despite a continuous flux of membranes between these domains. The Na(+)/H(+)exchanger NHE6 localizes to endosomes but its function is unknown. Here, we demonstrate that polarized hepatoma HepG2 cells express an NHE6.1 variant that localizes to recycling endosomes and colocalizes with transcytosing bulk membrane lipids. NHE6.1 knockdown or overexpression decreases or increases recycling endosome pH, respectively, and inhibits the maintenance of apical, bile canalicular plasma membranes and, concomitantly, apical lumens. NHE6.1 knockdown or overexpression has little effect on the de novo biogenesis of apical surface domains. NHE6.1 knockdown does not inhibit basolateral-to-apical transcytosis of bulk membrane lipids, but it does promote their progressive loss from the apical surface, leaving cells unable to efficiently retain bulk membrane and bile canalicular proteins at the apical surface. The data suggest that a limited range of endosome pH mediated by NHE6.1 is important for securing the polarized distribution of membrane lipids at the apical surface and maintenance of apical bile canaliculi in HepG2 cells and hence cell polarity. This study underscores the emerging role of the endosomal recycling system in apical surface development and identifies NHE6 as a novel regulatory protein in this process.
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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 Socratic graph.