A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis

Fenestrae are transcellular plasma membrane pores that mediate blood–tissue exchange in specialised vascular endothelia. The composition and biogenesis of the fenestra remain enigmatic. We isolated and characterised the protein composition of large patches of fenestrated plasma membrane, termed siev...

Full description

Bibliographic Details
Main Authors:	Meihua Ju, Sofia Ioannidou, Peter Munro, Olli Rämö, Helena Vihinen, Eija Jokitalo, David T. Shima
Format:	Article
Language:	English
Published:	MDPI AG 2020-06-01
Series:	Cells
Subjects:	fenestrae moesin annexin II actin fodrin Na,K-ATPase
Online Access:	https://www.mdpi.com/2073-4409/9/6/1387

id	doaj-46e05cb203e54d9699ba15da35a6b7a8
record_format	Article
spelling	doaj-46e05cb203e54d9699ba15da35a6b7a82020-11-25T02:49:37ZengMDPI AGCells2073-44092020-06-0191387138710.3390/cells9061387A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra BiogenesisMeihua Ju0Sofia Ioannidou1Peter Munro2Olli Rämö3Helena Vihinen4Eija Jokitalo5David T. Shima6Translational Vision Research, UCL Institute of Ophthalmology, London EC1v 9EL, UKEdmond de Rothschild Group, 75401 Paris, FranceElectron Microscopy Unit, UCL Institute of Ophthalmology, London EC1v 9EL, UKCell and Molecular Biology Program, University of Helsinki, 00014 Helsinki, FinlandElectron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, FinlandCell and Molecular Biology Program, University of Helsinki, 00014 Helsinki, FinlandTranslational Vision Research, UCL Institute of Ophthalmology, London EC1v 9EL, UKFenestrae are transcellular plasma membrane pores that mediate blood–tissue exchange in specialised vascular endothelia. The composition and biogenesis of the fenestra remain enigmatic. We isolated and characterised the protein composition of large patches of fenestrated plasma membrane, termed sieve plates. Loss-of-function experiments demonstrated that two components of the sieve plate, moesin and annexin II, were positive and negative regulators of fenestra formation, respectively. Biochemical analyses showed that moesin is involved in the formation of an actin–fodrin submembrane cytoskeleton that was essential for fenestra formation. The link between the fodrin cytoskeleton and the plasma membrane involved the fenestral pore protein PV-1 and Na,K-ATPase, which is a key regulator of signalling during fenestra formation both in vitro and in vivo. These findings provide a conceptual framework for fenestra biogenesis, linking the dynamic changes in plasma membrane remodelling to the formation of a submembrane cytoskeletal signalling complex.https://www.mdpi.com/2073-4409/9/6/1387fenestraemoesinannexin IIactinfodrinNa,K-ATPase
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Meihua Ju Sofia Ioannidou Peter Munro Olli Rämö Helena Vihinen Eija Jokitalo David T. Shima
spellingShingle	Meihua Ju Sofia Ioannidou Peter Munro Olli Rämö Helena Vihinen Eija Jokitalo David T. Shima A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis Cells fenestrae moesin annexin II actin fodrin Na,K-ATPase
author_facet	Meihua Ju Sofia Ioannidou Peter Munro Olli Rämö Helena Vihinen Eija Jokitalo David T. Shima
author_sort	Meihua Ju
title	A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis
title_short	A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis
title_full	A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis
title_fullStr	A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis
title_full_unstemmed	A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis
title_sort	na,k-atpase–fodrin–actin membrane cytoskeleton complex is required for endothelial fenestra biogenesis
publisher	MDPI AG
series	Cells
issn	2073-4409
publishDate	2020-06-01
description	Fenestrae are transcellular plasma membrane pores that mediate blood–tissue exchange in specialised vascular endothelia. The composition and biogenesis of the fenestra remain enigmatic. We isolated and characterised the protein composition of large patches of fenestrated plasma membrane, termed sieve plates. Loss-of-function experiments demonstrated that two components of the sieve plate, moesin and annexin II, were positive and negative regulators of fenestra formation, respectively. Biochemical analyses showed that moesin is involved in the formation of an actin–fodrin submembrane cytoskeleton that was essential for fenestra formation. The link between the fodrin cytoskeleton and the plasma membrane involved the fenestral pore protein PV-1 and Na,K-ATPase, which is a key regulator of signalling during fenestra formation both in vitro and in vivo. These findings provide a conceptual framework for fenestra biogenesis, linking the dynamic changes in plasma membrane remodelling to the formation of a submembrane cytoskeletal signalling complex.
topic	fenestrae moesin annexin II actin fodrin Na,K-ATPase
url	https://www.mdpi.com/2073-4409/9/6/1387
work_keys_str_mv	AT meihuaju anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT sofiaioannidou anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT petermunro anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT olliramo anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT helenavihinen anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT eijajokitalo anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT davidtshima anakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT meihuaju nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT sofiaioannidou nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT petermunro nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT olliramo nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT helenavihinen nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT eijajokitalo nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis AT davidtshima nakatpasefodrinactinmembranecytoskeletoncomplexisrequiredforendothelialfenestrabiogenesis
_version_	1724742390155051008

A Na,K-ATPase–Fodrin–Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis

Similar Items