ArticleMolecular biology of the cell2011
Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Acid-Base homeostasis in the brain: regional heterogeneity and different Acid-Base transporters.Pflugers Archiv : European journal of physiology · 2026Review
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Effects of Inhibitors of SLC9A-Type Sodium-Proton Exchangers onMolecular pharmacology · 2022Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Article
- Decreased Brain pH and Pathophysiology in Schizophrenia.International journal of molecular sciences · 2021Review
- Parrot Genomes and the Evolution of Heightened Longevity and Cognition.Current biology : CB · 2018Article
- Protons as Messengers of Intercellular Communication in the Nervous System.Frontiers in cellular neuroscience · 2018Review
- Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model.eLife · 2016Article
- Endosomal Na+/H+ exchanger NHE5 influences MET recycling and cell migration.Molecular biology of the cell · 2016Article
- Activity-regulated trafficking of the palmitoyl-acyl transferase DHHC5.Nature communications · 2015Article
- Na(+)/H(+) exchange and hypoxic pulmonary hypertension.Pulmonary circulation · 2015Review
- Molecular Mechanism for the Control of Eukaryotic Elongation Factor 2 Kinase by pH: Role in Cancer Cell Survival.Molecular and cellular biology · 2015Article
- Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.The Journal of biological chemistry · 2014Article
- Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity.Nature neuroscience · 2014Article
- Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5.Frontiers in physiology · 2014Review
- Secretory Carrier Membrane Protein (SCAMP) deficiency influences behavior of adult flies.Frontiers in cell and developmental biology · 2014Article
- Intracellular pH regulation by acid-base transporters in mammalian neurons.Frontiers in physiology · 2014Review
- Traditional and emerging roles for the SLC9 Na+/H+ exchangers.Pflugers Archiv : European journal of physiology · 2014Review
- Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling.Molecular biology of the cell · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Subtle changes in cellular and extracellular pH within the physiological range have profound impacts on synaptic activities. However, the molecular mechanisms underlying local pH regulation at synapses and their influence on synaptic structures have not been elucidated. Dendritic spines undergo dynamic structural changes in response to neuronal activation, which contributes to induction and long-term maintenance of synaptic plasticity. Although previous studies have indicated the importance of cytoskeletal rearrangement, vesicular trafficking, cell signaling, and adhesion in this process, much less is known about the involvement of ion transporters. In this study we demonstrate that N-methyl-D-aspartate (NMDA) receptor activation causes recruitment of the brain-enriched Na(+)/H(+) exchanger NHE5 from endosomes to the plasma membrane. Concomitantly, real-time imaging of green fluorescent protein-tagged NHE5 revealed that NMDA receptor activation triggers redistribution of NHE5 to the spine head. We further show that neuronal activation causes alkalinization of dendritic spines following the initial acidification, and suppression of NHE5 significantly retards the activity-induced alkalinization. Perturbation of NHE5 function induces spontaneous spine growth, which is reversed by inhibition of NMDA receptors. In contrast, overexpression of NHE5 inhibits spine growth in response to neuronal activity. We propose that NHE5 constrains activity-dependent dendritic spine growth via a novel, pH-based negative-feedback mechanism.
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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.