ArticleThe EMBO journal2001
Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 159 citations in OpenAlex.
- A pan-vertebrate signaling motif controls the molecular function of intracellular AQP12.The Journal of cell biology · 2026Article
- LRBA organizes distinct vesicular trafficking systems in distal nephron segments for water and sodium conservation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Aquaporin-4 downregulation in dysphagic patients with idiopathic inflammatory myopathies: myofiber vulnerability and inflammation drivers.Rheumatology (Oxford, England) · 2025Article
- AQP4 Endocytosis-Lysosome Degradation Mediated by MMP-9/β-DG Involved in Diabetes Cognitive Impairment.Molecular neurobiology · 2024Article
- SCFAutophagy · 2024Article
- Mechanisms of aquaporin-4 vesicular trafficking in mammalian cells.Journal of neurochemistry · 2024Article
- Ice plant root plasma membrane aquaporins are regulated by clathrin-coated vesicles in response to salt stress.Plant physiology · 2023Article
- Aquaporin Gating: A New Twist to Unravel Permeation through Water Channels.International journal of molecular sciences · 2022Review
- Insight into the Mammalian Aquaporin Interactome.International journal of molecular sciences · 2022Review
- The Readthrough Isoform AQP4ex Is Constitutively Phosphorylated in the Perivascular Astrocyte Endfeet of Human Brain.Biomolecules · 2022Article
- Molecular mechanisms governing aquaporin relocalisation.Biochimica et biophysica acta. Biomembranes · 2022Review
- C-Terminal Domain of Aquaporin-5 Is Required to Pass Its Protein Quality Control and Ensure Its Trafficking to Plasma Membrane.International journal of molecular sciences · 2021Article
- The Laminin-Induced Phosphorylation of PKCδ Regulates AQP4 Distribution and Water Permeability in Rat Astrocytes.Cellular and molecular neurobiology · 2021Article
- Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation.Molecular psychiatry · 2021Article
- Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development.eLife · 2020Article
- Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS.International journal of molecular sciences · 2020Article
- Review
- Role of the Golgi Apparatus in the Blood-Brain Barrier: Golgi Protection May Be a Targeted Therapy for Neurological Diseases.Molecular neurobiology · 2018Review
- Dileucine-like motifs in the C-terminal tail of connexin32 control its endocytosis and assembly into gap junctions.Journal of cell science · 2018Article
- Plant and Mammal Aquaporins: Same but Different.International journal of molecular sciences · 2018Review
4 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aquaporin 4 (AQP4) is the predominant water channel in the brain. It is targeted to specific membrane domains of astrocytes and plays a crucial role in cerebral water balance in response to brain edema formation. AQP4 is also specifically expressed in the basolateral membranes of epithelial cells. However, the molecular mechanisms involved in its polarized targeting and membrane trafficking remain largely unknown. Here, we show that two independent C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells. One signal involves a tyrosine-based motif; the other is encoded by a di-leucine-like motif. We found that the tyrosine-based basolateral sorting signal also determines AQP4 clathrin-dependent endocytosis through direct interaction with the mu subunit of AP2 adaptor complex. Once endocytosed, a regulated switch in mu subunit interaction changes AP2 adaptor association to AP3. We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression.
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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.