Cited by 94Ion channel regulation and functionCellular transport and secretionIon Transport and Channel Regulation

Endocytosis as a Mechanism for Tyrosine Kinase-dependent Suppression of a Voltage-gated Potassium Channel

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Nesti, Edmund, Everill, Brian, Morielli, Anthony D.·2004·Molecular Biology of the Cell

Abstract

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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Crossref · 10.1091/mbc.e03-11-0788

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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
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
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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