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POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION
Fan, Yi

2009, Doctor of Philosophy, Case Western Reserve University, Pathology.
Cell migration is crucial for various physiological and pathologicalprocesses, including embryonic morphogenesis, wound healing, immune
responses, cancer progression, and atherosclerosis development. Particularly,
endothelial cell (EC) migration is a fundamental process in angiogenesis and
vascular immune responses. Cell migration is driven by actin polymerization-mediated
lamellipodia protrusion, and proceeds by repeated cycles of protrusion,
adhesion, and contraction. Intensive studies have shown that these processes
are subjected to spatiotemporal regulation by signalling molecules, e.g. PI(3)K
and Rho GTPases, and by actin-binding proteins, e.g. Arp2/3 and cofilin. Here
our data show that 1) spatially restricted dissociation of G-actin–Tβ4 complexes
at the leading edge liberates actin for filament assembly, and simultaneously
facilitates Tβ4 binding to integrin-linked kinase in the lamellipodia, followed by
Akt2-mediated matrix metalloproteinase-2 production, providing a coordination
mechanism that couples actin polymerization to matrix degradation; 2) Myo1c
delivers lamellipodial G-actin to the leading edge to facilitate local actin
polymerization, indicating a mechanism for G-actin transport-mediated
polarization of actin polymerization; 3) During VEGF-induced endothelial cell
chemotaxis migration, profilin phosphorylation at Tyr129 preferentially occurs at
the leading edge to increase local actin polymerization, suggesting a mechanism
for establishment and maintenance of cell polarity during chemotaxis. Taken
together, these findings elucidate novel molecular mechanisms underlying
coordination of actin polymerization and matrix degradation, as well as
polarization of actin polymerization during EC migration, which contributes to
better molecular resolution of cell movement and may lead to the development of
therapeutic strategies for EC migration-related diseases.
Paul L Fox (Advisor)
Alan D Levine (Committee Chair)
Sanjay W Pimplikar (Committee Member)
Tom Egelhoff (Committee Member)
Clive Hamlin (Committee Member)
136 p.

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Fan, Y. (2009). POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Fan, Yi. "POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION." Electronic Thesis or Dissertation. Case Western Reserve University, 2009. OhioLINK Electronic Theses and Dissertations Center. 11 Dec 2017.

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Fan, Yi "POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION." Electronic Thesis or Dissertation. Case Western Reserve University, 2009. https://etd.ohiolink.edu/

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