A C-terminal PDZ binding domain modulates the function and localization of Kv1.3 channels

Autor: Anthony D. Morielli, Megan A. Doczi, Deborah H. Damon
Rok vydání: 2011
Předmět:
Tail
Sympathetic Nervous System
Recombinant Fusion Proteins
Mutant
PDZ domain
Golgi Apparatus
Biology
Transfection
complex mixtures
Article
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
Cell membrane
symbols.namesake
medicine
Animals
Humans
Protein Interaction Domains and Motifs
natural sciences
Golgi localization
Cells
Cultured
Sequence Deletion
Neurons
Kv1.3 Potassium Channel
urogenital system
Cell Membrane
Intracellular Signaling Peptides and Proteins
Wild type
Membrane Proteins
Arteries
Cell Biology
Golgi apparatus
Electrophysiological Phenomena
Rats
Transport protein
Cell biology
Protein Transport
HEK293 Cells
medicine.anatomical_structure
Animals
Newborn
nervous system
symbols
biological phenomena
cell phenomena
and immunity
Peptides
Disks Large Homolog 4 Protein
Oligopeptides
Binding domain
Zdroj: Experimental Cell Research. 317:2333-2341
ISSN: 0014-4827
DOI: 10.1016/j.yexcr.2011.06.009
Popis: The voltage-gated potassium channel, Kv1.3, plays an important role in regulating membrane excitability in diverse cell types ranging from T-lymphocytes to neurons. In the present study, we test the hypothesis that the C-terminal PDZ binding domain modulates the function and localization of Kv1.3. We created a mutant form of Kv1.3 that lacked the last three amino acids of the C-terminal PDZ-binding domain (Kv1.3ΔTDV). This form of Kv1.3 did not bind the PDZ domain containing protein, PSD95. We transfected wild type and mutant Kv1.3 into HEK293 cells and determined if the mutation affected current, Golgi localization, and surface expression of the channel. We found that cells transfected with Kv1.3ΔTDV had greater current and lower Golgi localization than those transfected with Kv1.3. Truncation of the C-terminal PDZ domain did not affect surface expression of Kv1.3. These findings suggest that PDZ-dependent interactions affect both Kv1.3 localization and function. The finding that current and Golgi localization changed without a corresponding change in surface expression suggests that PDZ interactions affect localization and function via independent mechanisms.
Databáze: OpenAIRE
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