Caveolin is Linked to Additional Sterol and Lipid Uptake and Trafficking Pathways

Several additional studies have indicated new roles for caveolin and associated proteins in the intracellular transport of cholesterol and the specific uptake of lipids. Caveolin-1 and SCP-2 directly interact in L-type fibroblasts, and co-localize both at the plasma membrane and in the cytosol [84]. The interplay between these nonvesicle trafficking pathways and vesicle-mediated transport in control of cholesterol trafficking and caveolae structure and organization will provide fruitful ground for further exploration.

Over a decade ago, caveolin was identified as a marker of caveolae and was found to be present in most cell types. Investigations of caveolae and lipid rafts over the past decade have resulted in more than 3500 publications which have brought tremendous change to our understanding of the organization of membranes and the functional organization of signaling and trafficking pathways within the cell. A new paradigm of the cell membrane consisting of multiple functional and structural domains has replaced the simple phospholipid bilayer model. This has also brought a conceptual paradigm shift of examining the integration of pathways linked through caveolae across the whole cell. The next frontier will involve the progression to models that are sufficiently sophisticated to provide a mechanistic understanding of the integration of pathways across tissues and organ systems. These investigations will be aided by use of cell- and tissue-specific knockout and knockin models which will, in turn, lead to a new level of integration in our understanding of the molecular events underlying diseases such as diabetes, inflammation, vascular disease, and cancer.

Abbreviations

cyp40

cyclophilin 40

cypA

cyclophilin A

eNOS

endothelial nitric oxide synthase

ER

endoplasmic reticulum

ER-GIC

endoplasmic reticulum-Golgi-intermediate-compartment

GPI

glycosyl-phosphatidylinositol

HDL

high-density lipoprotein

hsp

heat shock protein

HUVEC

human umbilical vein endothelial cells

LDL

low-density lipoprotein

PM

plasma membrane

SDS-

sodium dodecylsulfate-polyacryamide gel electrophoresis

PAGE

SR-BI

scavenger receptor BI

VVO

vesicular vacuolar organelle

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