Year: 2014
Type: other
Abstract: Physiological mechanotransduction experienced by the vasculature affects the expression of many actin-binding proteins that play an important role in endothelial cell function and the patho-physiology of cardiovascular disease (CVD).The expression of one such protein -Palladinplays an important role in cell cytoskeletal regulation, acting as a mediator for the regulation of vascular homeostasis through its unique protein-actin and protein-protein interactions.This study aims to elucidate the role for Palladin within the actin dynamics of the vasculature.Models mimicking the haemodynamic forces of cyclic strain and shear stress, acting on Human Aortic Endothelial Cells (HAECs) reveal that Palladin expression and localisation is mechanically altered within the vasculature.Protein expression increases especially as a result of both acute and chronic shear stress stimulation of the cell.Cellular fractionations of HAECs document the translocation of Palladin from the membrane to the cytoskeleton under laminar shear.Investigation of Palladin expression following culture of cells with extracellular matrices also suggest an integrin-mediated signalling of the protein.Following the shear stress-induced inflammatory response, the endothelial cells appear to export excess protein within secreted microparticles, complex structures which have been previously implicated in playing a role in inflammation and coagulation leading to impaired vascular function in CVDs.The presence of Palladin and two other proteins -LASP-1 and Drebrin-within these shear-induced microparticles is investigated here.Palladin appears to show an interaction with Drebrin (developmentally regulated brain protein), an actin-binding protein which itself is characterised in HAECs.Furthermore, the actin-binding, haemodynamically regulated protein -LASP-1 (Lim and Sh3 domain protein) was also investigated.Palladin is previously known to mediate the binding of LASP-1 to actin stress fibres.Here, we discuss the interactions between the three proteins, and also investigate the response of LASP-1 and Drebrin to haemodynamic force, namely shear stress.
Author: Ciaran McGinn
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W19012435