The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane
| Autor: | Vörös, Orsolya, Szilágyi, Orsolya, Balajthy, András, Somodi, Sándor, Panyi, György, Hajdu, Péter |
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| Rok vydání: | 2017 |
| Předmět: |
Kv1.3 Potassium Channel
Patch-Clamp Techniques lcsh:R Cell Membrane lcsh:Medicine Tetraethylammonium Orvostudományok CHO Cells Transfection complex mixtures Article Kinetics Cricetulus HEK293 Cells nervous system Animals Humans lcsh:Q Elméleti orvostudományok Amino Acid Sequence lcsh:Science Ion Channel Gating Conserved Sequence |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus. The truncation before the HRET sequence (NOHRET channels) resulted in reduced membrane-targeting but non-functional phenotypes. NOHRET channels did not display gating currents, and coexpression with wild-type Kv1.3 did not rescue the NOHRET-A413V phenotype, no heteromeric current was observed. Interestingly, mutants of wild-type Kv1.3 lacking HRET(E) (deletion) or substituted with five alanines for the HRET(E) motif expressed current indistinguishable from the wild-type. These results demonstrate that the C-terminal region of Kv1.3 immediately proximal to the S6 helix is required for the activation gating and conduction, whereas the presence of the distal region of the C-terminus is not exclusively required for trafficking of Kv1.3 to the plasma membrane. |
| Databáze: | OpenAIRE |
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