Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


case1247148451.pdf (15.08 MB)

ETD Abstract Container

Abstract Header

POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION

Fan, Yi
http://rave.ohiolink.edu/etdc/view?acc_num=case1247148451

Abstract Details

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.
Cellular Biology; Pathology
cell migration; endothelial cell; polarization; thymosin; profilin; myosin 1c

Recommended Citations

Citations

  • Fan, Y. (2009). POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1247148451

    APA Style (7th edition)

  • Fan, Yi. POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION. 2009. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1247148451.

    MLA Style (8th edition)

  • Fan, Yi. "POLARIZATION OF CYTOSKELETON-REGULATORY PROTEINS DURING ENDOTHELIAL CELL MIGRATION." Doctoral dissertation, Case Western Reserve University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1247148451

    Chicago Manual of Style (17th edition)

case1247148451
599
© 2009, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.