Academic Journal
Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome
| العنوان: | Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome |
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| المؤلفون: | Karlova, M., Abramochkin, D. V., Pustovit, K. B., Nesterova, T., Novoseletsky, V., Loussouarn, G., Zaklyazminskaya, E., Sokolova, O. S. |
| المصدر: | International Journal of Molecular Sciences |
| بيانات النشر: | MDPI |
| سنة النشر: | 2022 |
| المجموعة: | Ural Federal University (URFU): ELAR / Уральский федеральный университет: электронный архив УрФУ |
| مصطلحات موضوعية: | IKS, INHERITED CHANNELOPATHY, KCNQ1, KV7.1, LQTS, PATCH-CLAMP, KCNQ1 PROTEIN, HUMAN, POTASSIUM CHANNEL KCNQ1, AGED, CASE REPORT, GENETICS, HETEROZYGOTE, LONG QT SYNDROME, MALE, METABOLISM, MUTATION, POINT MUTATION, PRESCHOOL CHILD, CHILD, PRESCHOOL, HUMANS, KCNQ1 POTASSIUM CHANNEL |
| الوصف: | We identified a single nucleotide variation (SNV) (c.1264A > G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation. This missense mutation leads to a p.Lys422Glu (K422E) substitution in the Kv7.1 protein that has never been mentioned before. We inserted this substitution in an expression plasmid containing Kv7.1 cDNA and studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1, using the whole-cell configuration of the patch-clamp technique. Expression of the mutant Kv7.1 channel in both homo- and heterozygous conditions in the presence of auxiliary subunit KCNE1 results in a significant decrease in tail current densities compared to the expression of wild-type (WT) Kv7.1 and KCNE1. This study also indicates that K422E point mutation causes a dominant negative effect. The mutation was not associated with a trafficking defect; the mutant channel protein was confirmed to localize at the cell membrane. This mutation disrupts the poly-Lys strip in the proximal part of the highly conserved cytoplasmic A–B linker of Kv7.1 that was not shown before to be crucial for channel functioning. © 2022 by the authors. ; Russian Science Foundation, RSF: 22-14-00088; International Association for the Evaluation of Educational Achievement, IEA: 2773 ; This study was funded by Russian Science Foundation (22-14-00088 to O.S.S.). ; Authors thank Lisa Trifonova for proof-reading the manuscript and Lisha Mai for help with . G.L. would like to acknowledge support from the CNRS International Emerging Action (IEA) PRC RUSSIE 2019 (PRC no. 2773). O.S.S. and V.N. acknowledge the support from the Interdisciplinary Scientific and Educational School of Moscow Lomonosov University «Molecular Technologies of the Living Systems and Synthetic Biology». was created with the help of Biorender.com. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 16616596 |
| Relation: | info:eu-repo/grantAgreement/RSF//22-14-00088; Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome / M. Karlova, D. V. Abramochkin, K. B. Pustovit et al. // International Journal of Molecular Sciences. — 2022. — Vol. 23. — Iss. 14. — 7953.; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135102168&doi=10.3390%2fijms23147953&partnerID=40&md5=f1dba3eb7b0a72a47ef3c18d043b3681; http://elar.urfu.ru/handle/10995/118022; 85135102168; 000833279900001 |
| DOI: | 10.3390/ijms23147953 |
| الاتاحة: | http://elar.urfu.ru/handle/10995/118022 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135102168&doi=10.3390%2fijms23147953&partnerID=40&md5=f1dba3eb7b0a72a47ef3c18d043b3681 https://doi.org/10.3390/ijms23147953 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CE8A0007 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16616596 |
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| DOI: | 10.3390/ijms23147953 |