Endocytosis as a Mechanism for Tyrosine Kinase-dependent Suppression of a Voltage-gated Potassium Channel
Open accessAbstract
The voltage-gated potassium channel Kv1.2 undergoes tyrosine phosphorylation-dependent suppression of its ionic current. However, little is known about the physical mechanism behind that process. We have found that the Kv1.2 alpha-subunit protein undergoes endocytosis in response to the same stimuli that evoke suppression of Kv1.2 ionic current. The process is tyrosine phosphorylation-dependent because the same tyrosine to phenylalanine mutation in the N-terminus of Kv1.2 that confers resistance to channel suppression (Y132F) also confers resistance to channel endocytosis. Overexpression of a dominant negative form of dynamin blocked stimulus-induced Kv1.2 endocytosis and also blocked suppression of Kv1.2 ionic current. These data indicate that endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases.
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Activation of receptors promotes posttranslational modification of ion channels and recruitment of mediators including ubiquitin ligases and β-arrestins, which are key components of ion channel endocytosis.
“In brief, the activation of receptors promotes the posttranslational modification (PTM) of IChs and recruitment of mediators including ubiquitin ligases and β-arrestins, which are the key components of ion channel endocytosis [92,93].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [92]
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- Authors
- Nesti, E., Everill, B., & Morielli, A. D.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Morielli, Anthony D.
- Venue
- Molecular Biology of the Cell
- Published
- 2004-09
- Volume
- 15
- Issue
- 9
- Pages
- 4073-4088
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC515342
- OpenAlex
- W2165290124
- Cited by
- 94
- References
- 70
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30CA022435, P30-CA 22435)
- National Center for Research Resources (1P20RR16435, P20RR016435)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- Kv1.2, voltage-gated potassium channels, endocytosis, tyrosine phosphorylation, tyrosine kinase, ionic currents, dynamin, cell surface
- MeSH terms
- Animals, Antibodies, Monoclonal, Carbachol, Cell Line, Endocytosis, Humans, Protein-Tyrosine Kinases, Recombinant Proteins, Transfection, Vanadates, Mutagenesis, Site-Directed, Amino Acid Substitution, Potassium Channels, Voltage-Gated, Dynamins, Rats, Kv1.2 Potassium Channel, In Vitro Techniques
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