Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function.

Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. Research Abstract Details 

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Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. Abstract Text:

Pascal N Bernatchez,Lisette Acevedo,Carlos Fernandez-Hernando,Takahisa Murata,Cecile Chalouni,Jiae Kim,Hediye Erdjument-Bromage,Vijay Shah,Jean-Philippe Gratton,Elizabeth M McNally,Paul Tempst,William C Sessa,Pascal N Bernatchez,Lisette Acevedo,Carlos Fernandez-Hernando,Takahisa Murata,Cecile Chalouni,Jiae Kim,Hediye Erdjument-Bromage,Vijay Shah,Jean-Philippe Gratton,Elizabeth M McNally,Paul Tempst,William C Sessa,

Myoferlin and dysferlin are members of the ferlin family of membrane proteins. Recent studies have shown that mutation or genetic disruption of myoferlin or dysferlin promotes muscular dystrophy-related phenotypes in mice, which are the result of impaired plasma membrane integrity. However, no biological functions have been ascribed to myoferlin in non-muscle tissues. Herein, using a proteomic analysis of endothelial cell (EC) caveolae/lipid raft microdomains we identified myoferlin in these domains and show that myoferlin is highly expressed in ECs and vascular tissues. The loss of myoferlin results in lack of proliferation, migration, and nitric oxide (NO) release in response to vascular endothelial growth factor (VEGF). Western blotting and surface biotinylation experiments show that loss of myoferlin reduces the expression level and autophosphorylation of VEGF receptor-2 (VEGFR-2) in native ECs. In a reconstituted cell system, transfection of myoferlin increases VEGFR-2 membrane expression and autophosphorylation in response to VEGF. In vivo, VEGFR-2 levels and VEGF-induced permeability are impaired in myoferlin-deficient mice. Mechanistically, myoferlin forms a complex with dynamin-2 and VEGFR-2, which prevents CBL-dependent VEGFR-2 polyubiquitination and proteasomal degradation. These data are the first to report novel biological activities for myoferlin and reveal the role of membrane integrity to VEGF signaling.

Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. Publishing Authors By Initials

PN Bernatchez,L Acevedo,C Fernandez-Hernando,T Murata,C Chalouni,J Kim,H Erdjument-Bromage,V Shah,JP Gratton,EM McNally,P Tempst,WC Sessa,PN Bernatchez,L Acevedo,C Fernandez-Hernando,T Murata,C Chalouni,J Kim,H Erdjument-Bromage,V Shah,JP Gratton,EM McNally,P Tempst,WC Sessa,

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Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 30745-53

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 16

MONTH: 08

YEAR: 2007

Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function.

AFFILIATION: Department of Pharmacology and Vascular Biology & Transplantation Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL61371

ACRONYM: HL

MEDLINETA: J Biol Chem

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