Heteromeric complexes of aldo-keto reductase auxiliary KVβ subunits (AKR6A) regulate sarcolemmal localization of KV1.5 in coronary arterial myocytes
| Autor: | Ganapathy Jagatheesan, Deqing Zhang, Aruni Bhatnagar, Matthew A. Nystoriak |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Vascular smooth muscle Protein subunit Aldo-Keto Reductases Gating Biology Toxicology complex mixtures Article 03 medical and health sciences Kv1.5 Potassium Channel Mice Sarcolemma Myocyte Animals Myocytes Cardiac RNA Messenger Membrane potential Mice Knockout Cofactor binding Microscopy Confocal General Medicine Molecular biology Coronary Vessels Potassium channel Cell biology Isoenzymes Mice Inbred C57BL Protein Subunits 030104 developmental biology |
| Popis: | Redox-sensitive potassium channels consisting of the voltage-gated K+ (KV) channel pore subunit KV1.5 regulate resting membrane potential and thereby contractility of vascular smooth muscle cells. Members of the KV1 family associate with cytosolic auxiliary β subunits, which are members of the aldo-keto reductase (AKR) superfamily (AKR6A subfamily). The Kvβ subunits have been proposed to regulate Kv1 gating via pyridine nucleotide cofactor binding. However, the molecular identity of KVβ subunits that associate with native KV1.5 channels in the vasculature is unknown. Here, we examined mRNA and protein expression of KVβ subunits and tested whether KVβ isoforms interact with KV1.5 channels in murine coronary arteries. We detected KVβ1 (AKR6A3), KVβ2 (AKR6A5) and KVβ3 (AKR6A9) transcripts and KVβ1 and KVβ2 protein in left anterior descending coronary arteries by real time quantitative PCR and Western blot, respectively. In situ proximity ligation assays indicated abundant protein-protein interactions between KV1.5/KVβ1, KV1.5/KVβ2 and KVβ1/β2 in coronary arterial myocytes. Confocal microscopy and membrane fractionation analyses suggest that arterial myocytes from KVβ2-null mice have reduced abundance of sarcolemmal KV1.5. Together, data suggest that in coronary arterial myocytes, KV1.5 channels predominantly associate with KVβ1 and KVβ2 proteins and that KVβ2 performs a chaperone function for KV1.5 channels in arterial myocytes, thereby facilitating Kv1α trafficking and membrane localization. |
| Databáze: | OpenAIRE |
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