Biomedical Engineering Reference
In-Depth Information
and activates Rab8 GTPase. 11 Activation of Rab8 is antagonized by Rab8GAP
TBC1D30 (Vol. 4 - Chap. 9. Guanosine Triphosphatases and Their Regulators). 12
Small Rab11a GTPase and possibly Rab8 recruit the exocyst subunit Sec15a that
promotes the binding of the exocytic carrier to the Sec10 exocyst subunit on the
emerging AMIS membrane. Exocytosis also permits the initial recruitment of the
Par3-aPKC complex to AMIS sites. Active Rab8 stimulates CDC42 interaction with
the exocytic carriers, probably via CDC42GEF DnmBP or Tuba. 13 Small GTPase
CDC42 recruits atypical protein kinase-C that further promotes AMIS formation
and exocytosis, as it recruits exocyst protein Sec10 and Sec8 as well as Par3 that
colocalizes with Sec8 protein.
10.3
Arteriogenesis
Once the lumen of a main artery is strongly narrowed, the lumen of small arteries
increases to form collaterals that can maintain the blood perfusion. Arteriogenesis
is defined as the remodeling of a part of a pre-existing arterial network outside an
ischemic region to form functional irrigation arteries.
Arteriogenesis is initiated by CCL2 chemokine. Chemoattractant CCL2 stimu-
lates the formation of a collateral circulation on arterial occlusion [ 1181 ]. Arterio-
genesis thus involves inflammation with monocyte recruitment.
Various substances are also required at different stages of arteriogenesis, among
these, TGF
. Attracted monocytes produce
fibronectin and proteoglycans as well as peptidases to remodel the extracellular ma-
trix. These inflammatory cells then produce growth factors to stimulate proliferation
of endothelial and smooth muscle cells.
β
, PDGF, FGF2, CSF2, and TNF
α
11 Rab8 GTPase modulates polarized membrane transport via reorganization of actin and mi-
crotubules. Rab8 GTPase regulates membrane transport associated with TNF
α
-mediated stress
responses and cell morphogenesis [ 1179 ].
12 TBC (Tre2 proto-oncogene [ubiquitin-specific peptidase USP6], BUB2 [budding uninhibited by
benzimidazoles], and CDC16) motif-containing proteins pertains to GTPase activators of Rab and
Rab-like GTPases.
13 The CDC42-specific GEF dynamin-binding protein (DnmBP; a.k.a. Tuba according to the
tradition of naming large synaptic proteins after musical instruments) concentrates at the apical
region of cell junctions in epithelia via its interaction with zonula occludens protein ZO1. Scaffold
Tuba links dynamin, Rho GTPase, and the actin cytoskeleton. It connects dynamin to numerous
actin regulators [ 1180 ].
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