%0 Journal Article
%T Myosin VI and Associated Proteins Are Expressed in Human Macrophages but Do Not Play a Role in Foam Cell Formation in THP-1 Cells
%A Hayley J. Dawson
%A Andrew P. Hibbert
%A Peter D. Chantler
%A Kathleen M. Botham
%J International Journal of Vascular Medicine
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/516015
%X Myosin VI (Myo6) functions in endocytosis in conjunction with binding partners including adaptor protein (AP)-2, disabled 2 (Dab2), and GAIP interacting protein C terminus 1 (GIPC1). This study aimed to investigate the expression and function of Myo6 in macrophages and its possible role in the endocytosis of lipoproteins during the induction of foam cell formation. Expression of Myo6, AP-2 (¦Á2 subunit), and Dab2 in THP-1 macrophages and primary human monocyte-derived macrophages was demonstrated at the mRNA and protein level, but GIPC1 was only detected at the mRNA level. Immunofluorescence showed that Myo6 was distributed similarly to F-actin in both macrophage types. AP-2¦Á2 was found to have a similar subcellular distribution to Myo6 and Dab2 in THP-1 cells. Myo6 was located within membrane ruffles and protrusions of the plasma membrane. These results suggest that in macrophages Myo6 is required for several functions including cell adhesion, cell progression, and macropinocytosis. Low-density lipoprotein (LDL) and oxidised LDL (oxLDL) decreased Myo6 and GIPC1 mRNA expression in THP-1 cells, but uptake of the fluorescence-labelled lipoproteins was unaffected by knockdown of the expression of Myo6 or associated proteins with siRNA. Our findings, therefore, do not support the idea that Myo6 plays a major role in foam cell formation. 1. Introduction The uptake of large amounts of lipids from plasma lipoproteins via endocytosis by macrophages in the artery wall to form lipid-engorged foam cells is an important initiating event in the development of atherosclerosis, a major cause of heart disease. The main lipoprotein implicated is low-density lipoprotein (LDL), but oxidative modification of the particles, a process which can occur within the vessel wall, is required before foam cell formation is induced [1]. The myosin superfamily is a group of actin-associated motor proteins that use ATP hydrolysis to generate force or directional movement along actin filaments [2, 3]. Many new classes of myosin have been identified since the discovery, over seventy years ago, of myosin II (ˇ°conventionalˇ± myosin), which produces contractile force in muscle cells; to date, 35 classes of myosin proteins have been characterised in mammalian cells [4]. It is now known that these various classes of myosin motor are involved in a diverse range of intracellular processes, ranging from cell migration and division to cell anchorage and transport of cargo proteins along actin filaments [3]. Myosin VI (Myo6), a member of the ˇ°unconventionalˇ± myosin classes, is an unusual member of
%U http://www.hindawi.com/journals/ijvm/2013/516015/