Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 517

Constituents of endocytic vesicles include caveolin in addition to dynamin and
intersectin. The caveolin family includes 3 gene products (Cav1-Cav3). Caveolin-
1 is the major component of caveolae. Caveolin-1 has 2 isoforms. Caveolin-1
and -2 are coexpressed in many cell types, especially in endothelial cells, smooth
myocytes, fibroblasts, and adipocytes, whereas caveolin-3 is a muscle-specific type.
Endothelial cells from brain microvessels as well as type-2 alveolar epithelial cells
express caveolin-1, but have relatively few caveolae. Otherwise, caveola number is
correlated with caveolin-1 concentration.
Caveola genesis that requires caveolin-1 occurs by plasmalemmal lipid
remodeling into specialized membrane nanodomains rich in cholesterol and
sphingolipids. Caveolin-1 binds with high affinity to cholesterol, sphingolipids,
sphingomyelin, and glycosphingolipids [ 854 ]. Plasmalemmal cholesterol regulates
expression of caveolin-1 and caveola assembly. Caveolin-1 forms oligomers of 14 to
16 monomers in caveolae.
Caveolin-1 self-assembly begins in the endoplasmic reticulum. Post-translational
modifications of monomeric caveolin-1 (acylation, palmitoylation, and phosphory-
lation) and conjugation of glycosphingolipids facilitates caveolin-1 oligomerization.
Cholesterol is needed for caveolin-1 oligomerization and recruitment to the plasma
membrane. Oligomerized caveolin-1 stabilized by membrane cholesterol generates
caveolae owing to cofactors such as small Ras GTPase, whereas large GTPase
dynamin recruited by intersectin releases caveolae from the plasma membrane.
Caveolin-1 interacts with diverse signaling molecules, such as EGFR and
PDGFR receptors, Gq and other GTP-binding proteins, Src and PKC kinases,

IP 3 RandTRPC1Ca 2 + channels, and nitric oxide synthase NOS3. Caveolin-1
inhibits NOS3 enzyme. Caveolin-1 regulates activity of Rac GTPase and matrix
metallopeptidase.
Caveolin-1 favors association of

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-catenin with cadherin, thereby promoting
the assembly of adherens junction complex and contributing to the endothelial
paracellular barrier.
In endothelial cells, cortical actin barrier that is integrated with the plasma
membrane must be crossed by vesicles that carry various types of molecules. How-
ever, actin participates in caveola-mediated transport, as localized actin polymeriza-
tion occurs at sites of caveola fission. Dynamin interacts with actin-polymerizing
proteins of cortical actin filaments, such as the ARP2-ARP3 complex, cortactin,
filamin, profilin, and WASP, as well as adaptor GRB2. Therefore, dynamin is able
to control actin dynamics required for transport of released caveolae. Actin-related
nanomotor myosin serves to carry vesicles in the cell periphery in both anterograde
and retrograde direction with respect to plasma membrane. Microtubules also drive
caveola motion within the endothelial cell owing to their nanomotors kinesins
and dyneins.

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