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

English version

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: https://doi.org/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

Zdroje

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

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