ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Role of ubiquitylation and USP8-dependent deubiquitylation in the endocytosis and lysosomal targeting of plasma membrane KCa3.1.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.PNAS nexus · 2025Article
- Research progress of deubiquitinating enzymes in cerebral ischemia-reperfusion injury.Frontiers in aging neuroscience · 2025Review
- The exocyst complex is required for the trafficking and delivery of KCa3.1 to the basolateral membrane of polarized epithelia.American journal of physiology. Cell physiology · 2023Article
- Role of SNARE Proteins in the Insertion of KCa3.1 in the Plasma Membrane of a Polarized Epithelium.Frontiers in physiology · 2022Article
- Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.The Journal of biological chemistry · 2021Review
- Ubiquitin-specific peptidase 8 regulates the trafficking and stability of the human organic anion transporter 1.Biochimica et biophysica acta. General subjects · 2020Article
- The Role of Deubiquitinating Enzymes in the Various Forms of Autophagy.International journal of molecular sciences · 2020Review
- Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions.Biochemical Society transactions · 2019Review
- The Deubiquitinating Enzyme Inhibitor PR-619 is a Potent DNA Topoisomerase II Poison.Molecular pharmacology · 2019Article
- The intramembrane protease SPP impacts morphology of the endoplasmic reticulum by triggering degradation of morphogenic proteins.The Journal of biological chemistry · 2019Article
- Plasma membrane insertion of KCa2.3 (SK3) is dependent upon the SNARE proteins, syntaxin-4 and SNAP23.PloS one · 2018Article
- Structure, Gating and Basic Functions of the Ca2+-activated K Channel of Intermediate Conductance.Current neuropharmacology · 2018Review
- Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation.Scientific reports · 2017Article
- Modulation of Retrograde Trafficking of KCa3.1 in a Polarized Epithelium.Frontiers in physiology · 2017Article
- A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila.BMC cell biology · 2016Article
- The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation.The Journal of biological chemistry · 2016Article
- The Role of the Cytoskeleton and Myosin-Vc in the Targeting of KCa3.1 to the Basolateral Membrane of Polarized Epithelial Cells.Frontiers in physiology · 2016Article
- Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis.Molecular & cellular proteomics : MCP · 2015Article
- The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest.Molecular and cellular biology · 2015Article
- Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer's model.PLoS genetics · 2015Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
We recently demonstrated that plasma membrane KCa3.1 is rapidly endocytosed and targeted for lysosomal degradation via a Rab7- and ESCRT-dependent pathway. Herein, we assess the role of ubiquitylation in this process. Using a biotin ligase acceptor peptide (BLAP)-tagged KCa3.1, in combination with tandem ubiquitin binding entities (TUBEs), we demonstrate that KCa3.1 is polyubiquitylated following endocytosis. Hypertonic sucrose inhibited KCa3.1 endocytosis and resulted in a significant decrease in channel ubiquitylation. Inhibition of the ubiquitin-activating enzyme (E1) with UBEI-41 resulted in reduced KCa3.1 ubiquitylation and internalization. The general deubiquitylase (DUB) inhibitor, PR-619 attenuated KCa3.1 degradation, indicative of deubiquitylation being required for lysosomal delivery. Using the DUB Chip, a protein microarray containing 35 DUBs, we demonstrate a time-dependent association between KCa3.1 and USP8 following endocytosis, which was confirmed by coimmunoprecipitation. Further, overexpression of wild-type USP8 accelerates channel deubiquitylation, while either a catalytically inactive mutant USP8 or siRNA-mediated knockdown of USP8 enhanced accumulation of ubiquitylated KCa3.1, thereby inhibiting channel degradation. In summary, by combining BLAP-tagged KCa3.1 with TUBEs and DUB Chip methodologies, we demonstrate that polyubiquitylation mediates the targeting of membrane KCa3.1 to the lysosomes and also that USP8 regulates the rate of KCa3.1 degradation by deubiquitylating KCa3.1 prior to lysosomal delivery.
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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.