Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 518

Dynamin causes caveolar fission. Homotetrameric dynamin undergoes
GTP-dependent self-assembly that increases its intrinsic GTPase activity. Dynamin
oligomers generate a constricting force around vesicle collars that leads to

membrane fission and caveola internalization.
Intersectins regulate membrane fission and fusion of endothelial caveolae.
Intersectins are dynamin partners and regulators. Intersectin isoforms comprise
nerve-specific intersectin-1 and ubiquitous intersectin-2. The latter has 2 splice vari-
ants, short (intersectin-2 S ) and long (intersectin-2 L )forms. 83 Intersectin-2 is located
at necks of caveolae, where it can sequester dynamin dimers or tetramers [ 854 ].
Scaffold intersectin binds to Ca 2 + , phospholipids, inositol phosphates, WASP,
RasGEF Son of sevenless, CDC42 and Rac1 GTPase-activating protein RhoGAP31,
soluble N ethylmaleimide-sensitive factor attachment protein receptor (SNARE),
synaptosome-associated protein SNAP23 and SNAP25, and synaptojamin. Unlike
dynamin, intersectin remains associated with vesicles following fission.
Caveolae require vSNAREs and tSNAREs on vesicle and target membranes,
respectively. Vesicle docking and fusion involve syntaxin, Rab5, vesicle-associated
membrane protein (VAMP), 84 and N ethylmaleimide-sensitive factor (NSF). Mole-
cule NSF binds SNARE complex via soluble α -or β SNAP. Hexameric ATPase

NSF and SNAP are SNARE regulators that catalyze SNARE complex disassembly

following membrane fusion and liberate SNARE monomers for recycling [ 854 ].
Small GTPases of the RAB family regulate cellular transport. Endothelial cells
express Rab1 to Rab9, Rab11, Rab13 to Rab15, Rab18, Rab22, and Rab30 [ 854 ].
Caveola-associated proteins can regulate transcytosis. Endothelial macromolec-
ular transcytotic complex that comprises caveolin-1, dynamin, Rab5 GTPase,
N ethylmaleimide-sensitive factor, and syntaxin is involved in caveola fission, tar-
geting, docking, and fusion with the plasma membrane.
Kinase Src allows formation of the caveolin-1-dynamin complex after phosphor-
ylation of both dynamin and caveolin-1. Balance between tyrosine phosphorylation
and dephosphorylation of caveolin-1 and dynamin controls endocytosis. Protein
kinases PKC

α

α ,PKC β ,andPKC δ lodge in caveolae. Activation of these PKC

isoforms as well as PKC prevents caveola internalization [ 854 ].

Phosphatidylinositol 3-kinase is also involved in endocytosis.
Caveolae contain Ca 2 + -signaling elements, such as IP 3 R, store-operated Ca 2 +
channels, transient receptor potential channels TRPC1 and TRPC3, and Ca 2 + AT-
Pase [ 854 ]. Increase in intracellular Ca 2 + concentration induces exocytosis of
Weibel-Palade bodies.

and PKC γ

83 Intersectin-2 long form possesses a GEF domain that activates CDC42 GTPase, but neither Rac
nor RhoA GTPse.
84 A.k.a. synaptobrevin.