Biomedical Engineering Reference
In-Depth Information
interactions, PEST domains for protein turnover, and phosphorylation motifs. They
bind phosphatidylserine. They are phosphorylated upon insulin stimulation [
878
].
Cavin-1 colocalizes with Cav1 in membrane rafts, where they interact with
the cell cytoskeleton, especially cortical microtubules and actin filaments [
878
].
Cavin-1 sequesters caveolins into caveolae. Cavin-2 binds to and recruits cavin-1
to the plasma membrane. The cavin-1-cavin-2 complex stabilizes Cav1-containing
structures. Cavin-2 is a PKC substrate that is involved in PKC compartmentation
in caveolae. Cavin-3 supports budding and formation of cavicles. Cavin-4 is
predominantly in myocytes.
Dynamin-2 binds to Cav1 during Cav1-mediated endocytosis. Insulin receptor
as well as Src kinase phosphorylate Cav1 (Tyr14), in response to growth-factor
stimulation and cellular stress. Caveolin-1
P
interacts with C-terminal Src kinase to
preclude Src action [
878
].
9.5.1.2
Caveolae in Endothelium Functions
Caveolin-1 regulates microvascular permeability, Ca
2
+
influx, vascular remodeling,
and angiogenesis. Many G-protein-coupled receptors, receptor and cytosolic Tyr
kinases (e.g., EGFR), small GTPases, and components of the MAPK module
(e.g., Raf, ERK1, and ERK2) interact with Cav1 and reside in caveolae [
878
]. In
particular, caveolin-1 sequesters ERK1, and ERK2, thereby impeding the activity of
this pathway.
In addition, caveolin-1 contributes to integrin signaling, particularly
β
1
-integrin
localization to caveolae upon IGF stimulation. Caveolin-1 also tethers cyclo-
oxygenase-2 to the endoplasmic reticulum, hence promoting its degradation.
In vascular endothelial cells, caveolae participate in the regulation of the vascular
tone, as caveolin-1 in caveolae inhibits endothelial nitric oxide synthase (NOS3)
activity, but not caveolin-1 in non-caveolar membrane rafts [
878
]. Caveolin-1
and Ca
2
+
ions antagonistically regulate NOS3 in the microcirculation. However,
caveolin-1 participates in Ca
2
+
import into endothelial cells.
29
29
Many processes rely on Ca
2
+
ions, in particular inflammation and angiogenesis. Ca
2
+
signaling
can comprise 3 phases [
878
]: (1) rapid, initial Ca
2
+
influx by release from endoplasmic reticulum
store that can result from stimulated G-protein-coupled receptors and receptor protein Tyr kinases
via phospholipase-C activation and inositol trisphosphate; (2) sustained entry of extracellular Ca
2
+
ions through Ca
2
+
release-activated Ca
2
+
channels and receptor-operated Ca
2
+
channels; and
(3) tonic Ca
2
+
entry that permits long-term Ca
2
+
signal propagation and replenishes intracellular
Ca
2
+
stores.
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