ArticleMolecular biology of the cell2013
Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Acid-Base homeostasis in the brain: regional heterogeneity and different Acid-Base transporters.Pflugers Archiv : European journal of physiology · 2026Review
- Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot-Marie-Tooth 2B Disease.Biomolecules · 2023Review
- Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.Reviews of physiology, biochemistry and pharmacology · 2023Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Potentiometric pH Nanosensor for Intracellular Measurements: Real-Time and Continuous Assessment of Local Gradients.Analytical chemistry · 2021Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Bioenergetic Requirements and Spatiotemporal Profile of Nerve Growth Factor Induced PI3K-Akt Signaling Along Sensory Axons.Frontiers in molecular neuroscience · 2021Article
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- Pathobiology of Christianson syndrome: Linking disrupted endosomal-lysosomal function with intellectual disability and sensory impairments.Neurobiology of learning and memory · 2019Article
- GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury.BioMed research international · 2019Article
- Live-cell Microscopy and Fluorescence-based Measurement of Luminal pH in Intracellular Organelles.Frontiers in cell and developmental biology · 2017Article
- Article
- Endosomal Na+/H+ exchanger NHE5 influences MET recycling and cell migration.Molecular biology of the cell · 2016Article
- Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons.Frontiers in cellular neuroscience · 2016Article
- Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.Antimicrobial agents and chemotherapy · 2014Article
- Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury.Journal of translational medicine · 2014Article
- Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts.Journal of lipid research · 2014Article
- Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5.Frontiers in physiology · 2014Review
- Regulation of neurotrophin receptor (Trk) signaling: suppressor of cytokine signaling 2 (SOCS2) is a new player.Frontiers in molecular neuroscience · 2014Review
- Secretory Carrier Membrane Protein (SCAMP) deficiency influences behavior of adult flies.Frontiers in cell and developmental biology · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To facilitate polarized vesicular trafficking and signal transduction, neuronal endosomes have evolved sophisticated mechanisms for pH homeostasis. NHE5 is a member of the Na(+)/H(+) exchanger family and is abundantly expressed in neurons and associates with recycling endosomes. Here we show that NHE5 potently acidifies recycling endosomes in PC12 cells. NHE5 depletion by plasmid-based short hairpin RNA significantly reduces cell surface abundance of TrkA, an effect similar to that observed after treatment with the V-ATPase inhibitor bafilomycin. A series of cell-surface biotinylation experiments suggests that anterograde trafficking of TrkA from recycling endosomes to plasma membrane is the likeliest target affected by NHE5 depletion. NHE5 knockdown reduces phosphorylation of Akt and Erk1/2 and impairs neurite outgrowth in response to nerve growth factor (NGF) treatment. Of interest, although both phosphoinositide 3-kinase-Akt and Erk signaling are activated by NGF-TrkA, NGF-induced Akt-phosphorylation appears to be more sensitively affected by perturbed endosomal pH. Furthermore, NHE5 depletion in rat cortical neurons in primary culture also inhibits neurite formation. These results collectively suggest that endosomal pH modulates trafficking of Trk-family receptor tyrosine kinases, neurotrophin signaling, and possibly neuronal differentiation.
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