Caveolae and human disease: functional roles in transcytosis, potocytosis, signalling and cell polarity

Caveolae are 50–100 nm invaginations that represent a sub-compartment of the plasma membrane. Recent studies have implicated these membranous structures in: (1) transcytosis of macromolecules (such as LDL and AGEs) across capillary endothelial cells; (2) potocytic uptake of small molecules via GPI-linked receptors coupled with an unknown anion transport protein; (3) certain transmembrane signalling events; and (4) polarized trafficking of GPI-linked proteins in epithelial cells. Biochemical isolation and characterization of these domains reveals the molecular components that could perform these diverse functions: scavenger receptors for oxidized LDL and AGEs, namely CD 36 and RAGE, respectively (transcytosis); plasma membrane porin (potocytosis); heterotrimeric G-proteins and Src-like kinases (signalling); and Rap GTPases (cell polarity). As such, these findings have clear implications for understanding the molecular pathogenesis of several human diseases — including atherosclerosis, diabetic vascular complications, and cancerous cell transformations.