title: Annexin A2 is involved in Ca2+-dependent plasma membrane repair in primary human endothelial cells.
abstract: Many cells in an organism are exposed to constant and acute mechanical stress that can induce plasma membrane injuries. These plasma membrane wounds have to be resealed rapidly to guarantee cell survival. Plasma membrane resealing in response to mechanical strain has been studied in some detail in muscle, where it is required for efficient recovery after insult. However, less is known about the capacity of other cell types and tissues to perform membrane repair and the underlying molecular mechanisms. Here we show that vascular endothelial cells, which are subject to profound mechanical burden, can reseal plasma membrane holes inflicted by laser ablation. Resealing in endothelial cells is a Ca2+-dependent process, as it is inhibited when cells are wounded in Ca2+-free medium. We also show that annexin A1 (AnxA1), AnxA2 and AnxA6, Ca2+-regulated membrane binding proteins previously implicated in membrane resealing in other cell types, are rapidly recruited to the site of plasma membrane injury. S100A11, a known protein ligand of AnxA1, is also recruited to endothelial plasma membrane wounds, albeit with a different kinetic. Mutant expression experiments reveal that Ca2+binding to AnxA2, the most abundant endothelial annexin, is required for translocation of the protein to the wound site. Furthermore, we show by knock-down and rescue experiments that AnxA2 is a positive regulator of plasma membrane resealing. Thus, vascular endothelial cells are capable of active, Ca2+-dependent plasma membrane resealing and this process requires the activity of AnxA2.
authors.affiliation: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, 48149 Münster, Germany. Electronic address: s.koerdt@uni-muenster.de.
authors.forename: Sophia Nina
authors.initials: SN
authors.lastname: Koerdt
authors.affiliation: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, 48149 Münster, Germany. Electronic address: gerke@uni-muenster.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
mesh_terms: D017306:Annexin A2 / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans
chemical_list: D017306:Annexin A2; D002118:Calcium
keywords: Annexin; Calcium; Endothelium; Membrane