Discs large 1 (Dlg1) scaffolding protein participates with clathrin and adaptator protein complex 1 (AP-1) in forming Weibel-Palade bodies of endothelial cells. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2013

Discs large 1 (Dlg1) scaffolding protein participates with clathrin and adaptator protein complex 1 (AP-1) in forming Weibel-Palade bodies of endothelial cells.

Résumé

Weibel-Palade bodies (WPBs) are specific cigar-shaped granules that store von Willebrand factor (VWF) for its regulated secretion by endothelial cells. The first steps of the formation of these granules at the trans-Golgi network (TGN) specifically require VWF aggregation and an external scaffolding complex that contains the adaptator protein complex 1 (AP-1) and clathrin. Discs large 1 (Dlg1) is generally considered to be a modular scaffolding protein implicated in the control of cell polarity in a large variety of cells by specific recruiting of receptors, channels or signaling proteins to specialized zones of the plasma membrane. We propose here that in endothelial cells, Dlg1 in a complex with AP-1 and clathrin participates in the biogenesis of WPBs. Supporting data show that Dlg1 colocalizes with microtubules, intermediate filaments and Golgi markers. Tandem mass spectrometry experiments led to the identification of clathrin as a Dlg1-interacting partner, interaction was confirmed by in situ proximity ligation assays. Furthermore, AP-1 and VWF immunoprecipitate and colocalize with Dlg1 in the juxta-nuclear zone. Finally, Dlg1 depletion by siRNA duplexes disrupts TGN morphology and WPB formation. Our results provide the first evidence for an unexpected role of Dlg1 in controlling the formation of specific secretory granules involved in VWF exocytosis in endothelial cells.

Dates et versions

hal-00817404 , version 1 (24-04-2013)

Identifiants

Citer

Monique Philippe, Thibaut Leger, Raphaelle Desvaux, Laurence Walch. Discs large 1 (Dlg1) scaffolding protein participates with clathrin and adaptator protein complex 1 (AP-1) in forming Weibel-Palade bodies of endothelial cells.. Journal of Biological Chemistry, 2013, epub ahead of print. ⟨10.1074/jbc.M112.441261⟩. ⟨hal-00817404⟩
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