PMID- 34771134 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20211214 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 26 IP - 21 DP - 2021 Nov 6 TI - Subcellular Localization of Connexin 26 in Cardiomyocytes and in Cardiomyocyte-Derived Extracellular Vesicles. LID - 10.3390/molecules26216726 [doi] LID - 6726 AB - Connexins (Cxs) are a family of membrane-spanning proteins, expressed in vertebrates and named according to their molecular weight. They are involved in tissue homeostasis, and they function by acting at several communication levels. Cardiac Cxs are responsible for regular heart function and, among them, Cx26 and Cx43 are widely expressed throughout the heart. Cx26 is present in vessels, as well as in cardiomyocytes, and its localization is scattered all over the cell aside from at the intercalated discs as is the case for the other cardiac Cxs. However, having been found in cardiomyocytes only recently, both its subcellular localization and its functional characterization in cardiomyocytes remain poorly understood. Therefore, in this study we aimed to obtain further data on the localization of Cx26 at the subcellular level. Our TEM immunogold analyses were performed on rat heart ventricles and differentiated H9c2 cardiac cell sections as well as on differentiated H9c2 derived extracellular vesicles. The results confirmed the absence of Cx26 at intercalated discs and showed the presence of Cx26 at the level of different subcellular compartments. The peculiar localization at the level of extracellular vesicles suggested a specific role for cardiac Cx26 in inter-cellular communication in an independent gap junction manner. FAU - Falleni, Alessandra AU - Falleni A AUID- ORCID: 0000-0001-6492-6038 AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Moscato, Stefania AU - Moscato S AUID- ORCID: 0000-0001-9283-6902 AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Sabbatini, Antonietta R M AU - Sabbatini ARM AUID- ORCID: 0000-0002-6375-7778 AD - Department of Surgical, Medical, Molecular Pathology and of Emergency Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Bernardeschi, Margherita AU - Bernardeschi M AUID- ORCID: 0000-0003-2650-1834 AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Bianchi, Francesco AU - Bianchi F AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Cecchettini, Antonella AU - Cecchettini A AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. AD - Institute of Clinical Physiology (IFC), National Research Council (CNR), 56126 Pisa, Italy. FAU - Mattii, Letizia AU - Mattii L AUID- ORCID: 0000-0001-6835-7987 AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. LA - eng PT - Journal Article DEP - 20211106 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 127120-53-0 (Connexin 26) SB - IM MH - Animals MH - Cell Line MH - Connexin 26/*analysis/metabolism MH - Extracellular Vesicles/*chemistry/metabolism MH - Gap Junctions/chemistry/metabolism MH - Myocytes, Cardiac/*chemistry/metabolism MH - Rats PMC - PMC8587102 OTO - NOTNLM OT - H9c2 cells OT - cardiomyocyte OT - connexin26 OT - extracellular vesicles OT - immunoelectron microscopy OT - rat heart OT - ultrastructure COIS- The authors declare no conflict of interest. EDAT- 2021/11/14 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/11/06 CRDT- 2021/11/13 01:13 PHST- 2021/09/14 00:00 [received] PHST- 2021/10/26 00:00 [revised] PHST- 2021/11/03 00:00 [accepted] PHST- 2021/11/13 01:13 [entrez] PHST- 2021/11/14 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/11/06 00:00 [pmc-release] AID - molecules26216726 [pii] AID - molecules-26-06726 [pii] AID - 10.3390/molecules26216726 [doi] PST - epublish SO - Molecules. 2021 Nov 6;26(21):6726. doi: 10.3390/molecules26216726.