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Research Spotlight: Laboratory of Dudley Strickland, Ph.D.

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Laboratory of Dudley Strickland, Ph.D.
Anna Lillis (M.D, Ph.D Student Ph.D awarded 2007)
Irina Mikhailanko Ph.D., CVID Microscopy Core Facility 

Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability 

Journal of Thrombosis and Haemostasis 3 (8), 1884?1893.

The low-density lipoprotein (LDL) receptor related protein (LRP1 or LRP) is a large endocytic receptor widely expressed in several tissues and known to play roles in areas as diverse as lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. This member of the LDL receptor superfamily is constitutively endocytosed from the membrane and recycled back to the cell surface. Its many functions were long thought to involve its ability to bind over 30 different ligands and deliver them to lysosomes for degradation. However, LRP has since been shown to interact with scaffolding and signaling proteins via its intracellular domain in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. This multi-talented receptor has been implicated in regulation of platelet derived growth factor receptor activity, integrin maturation and recycling, and focal adhesion disassembly. These functions may account for recent studies identifying LRP's role in protection of the vasculature, regulation of cell migration, and modulation of the integrity of the blood–brain barrier.

research image

Expression of low-density lipoprotein receptor related protein (LRP) (top panels) and very low-density lipoprotein receptor (VLDLR) (bottom panels) in cultured cells. Rat brain capillary endothelial cells (VEC, left panels) or rat vascular smooth muscle cells (SMC, right panels) were cultured on glass slips coated with gelatin. The cells were fixed, permeabilized, and incubated with rabbit anti-LRP (top panels) or a mouse monoclonal antibody against the VLDLR (bottom panels). LRP (red) was detected by staining with an anti-rabbit Cy3-labeled IgG, while VLDLR (red) was detected by staining with anti-mouse IgG labeled with Alexa568. Green staining shows actin stained with FITC-phalloidin, while blue shows TO-PRO3 staining of DNA to identify nuclei. Bar is 20 ?m.