eNOS-NO-induced small blood vessel relaxation requires EHD2-dependent caveolae stabilization


Autoři: Claudia Matthaeus aff001;  Xiaoming Lian aff002;  Séverine Kunz aff003;  Martin Lehmann aff004;  Cheng Zhong aff002;  Carola Bernert aff001;  Ines Lahmann aff005;  Dominik N. Müller aff006;  Maik Gollasch aff002;  Oliver Daumke aff001
Působiště autorů: Crystallography, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany aff001;  Charité—Universitätsmedizin Berlin, Experimental and Clinical Research Center (ECRC), Campus Buch, Berlin, Germany aff002;  Electron Microscopy Core Facility, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany aff003;  Department of Molecular Pharmacology & Cell Biology and Imaging Core Facility, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany aff004;  Signal Transduction/Developmental Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany aff005;  Experimental & Clinical Research Center, a cooperation between Charité Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany aff006;  Charité—Universitätsmedizin Berlin, Medical Clinic for Nephrology and Internal Intensive Care, Campus Virchow, Berlin, Germany aff007;  Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223620

Souhrn

Endothelial nitric oxide synthase (eNOS)-related vessel relaxation is a highly coordinated process that regulates blood flow and pressure and is dependent on caveolae. Here, we investigated the role of caveolar plasma membrane stabilization by the dynamin-related ATPase EHD2 on eNOS-nitric oxide (NO)-dependent vessel relaxation. Loss of EHD2 in small arteries led to increased numbers of caveolae that were detached from the plasma membrane. Concomitantly, impaired relaxation of mesenteric arteries and reduced running wheel activity were observed in EHD2 knockout mice. EHD2 deletion or knockdown led to decreased production of nitric oxide (NO) although eNOS expression levels were not changed. Super-resolution imaging revealed that eNOS was redistributed from the plasma membrane to internalized detached caveolae in EHD2-lacking tissue or cells. Following an ATP stimulus, reduced cytosolic Ca2+ peaks were recorded in human umbilical vein endothelial cells (HUVECs) lacking EHD2. Our data suggest that EHD2-controlled caveolar dynamics orchestrates the activity and regulation of eNOS/NO and Ca2+ channel localization at the plasma membrane.

Klíčová slova:

Arteries – Cell membranes – Cell staining – Membrane proteins – Mouse models – Small interfering RNAs – Coated pits – Mesenteric arteries


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