Spire1 and Myosin Vc promote Ca2+-evoked externalization of von Willebrand factor in endothelial cells

Holthenrich, Anna and Terglane, Julian and Nass, Johannes and Mietkowska, Magdalena and Kerkhoff, Eugen and Gerke, Volker (2022) Spire1 and Myosin Vc promote Ca2+-evoked externalization of von Willebrand factor in endothelial cells. CELLULAR AND MOLECULAR LIFE SCIENCES, 79 (2): 96. ISSN 1420-682X, 1420-9071

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Abstract

Weibel-Palade bodies (WPB) are endothelial cell-specific storage granules that regulate vascular hemostasis by releasing the platelet adhesion receptor von Willebrand factor (VWF) following stimulation. Fusion of WPB with the plasma membrane is accompanied by the formation of actin rings or coats that support the expulsion of large multimeric VWF fibers. However, factor(s) organizing these actin ring structures have remained elusive. We now identify the actin-binding proteins Spire1 and Myosin Vc (MyoVc) as cytosolic factors that associate with WPB and are involved in actin ring formation at WPB-plasma membrane fusion sites. We show that both, Spire1 and MyoVc localize only to mature WPB and that upon Ca2+ evoked exocytosis of WPB, Spire1 and MyoVc together with F-actin concentrate in ring-like structures at the fusion sites. Depletion of Spire1 or MyoVc reduces the number of these actin rings and decreases the amount of VWF externalized to the cell surface after histamine stimulation.

Item Type: Article
Uncontrolled Keywords: WEIBEL-PALADE BODIES; DEPENDENT MECHANISM; ACTIN CYTOSKELETON; BODY EXOCYTOSIS; FACTOR RELEASE; RAB27A; MYRIP; SECRETION; MEMBRANE; IDENTIFICATION; Weibel-Palade bodies; Exocytosis; Endothelial activation; Calcium signaling; Actin nucleation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Feb 2024 14:59
Last Modified: 08 Feb 2024 14:59
URI: https://pred.uni-regensburg.de/id/eprint/58025

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