Academic Journal
Myosin VI facilitates connexin 43 gap junction accretion
| العنوان: | Myosin VI facilitates connexin 43 gap junction accretion |
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| المؤلفون: | Waxse, BJ, Sengupta, P, Hesketh, GG, Lippincott-Schwartz, J, Buss, F |
| بيانات النشر: | //doi.org/10.1242/jcs.199083 Journal of Cell Science The Company of Biologists |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | connexin, endocytosis, gap junction, myosin |
| الوصف: | In this study, we demonstrate myosin VI enrichment at Cx43 (also known as GJA1)-containing gap junctions (GJs) in heart tissue, primary cardiomyocytes and cell culture models. In primary cardiac tissue and in fibroblasts from the myosin VI-null mouse as well as in tissue culture cells transfected with siRNA against myosin VI, we observe reduced GJ plaque size with a concomitant reduction in intercellular communication, as shown by fluorescence recovery after photobleaching (FRAP) and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable for the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane. Furthermore, we cannot corroborate clathrin or Dab2 localization at gap junctions and we do not observe a function for the myosin-VI–Dab2 complex in clathrin-dependent endocytosis of annular gap junctions. Instead, we found that myosin VI was localized at the edge of Cx43 plaques by using total internal reflection fluorescence (TIRF) microscopy and use FRAP to identify a plaque accretion defect as the primary manifestation of myosin VI loss in Cx43 homeostasis. A fuller understanding of this derangement may explain the cardiomyopathy or gliosis associated with the loss of myosin VI. ; B.W. is a National Institutes of Health Oxford-Cambridge scholar supported by funding obtained by J.L.-S. from the Eunice Shriver National Institute of Child Health and Human Development. F.B. thanks the Wellcome Trust for funding of the Cambridge Institute for Medical Research (CIMR) Strategic Award (100140), an equipment grant (093026), the Medical Research Council (MR/K000888/1 and MR/N000048/1) and the British Heart Foundation for funding of the project grant (PG/15/12/31280). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://www.repository.cam.ac.uk/handle/1810/263163 |
| DOI: | 10.17863/CAM.8470 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/263163 https://doi.org/10.17863/CAM.8470 |
| Rights: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.4301AC89 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.8470 |
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