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Detachment versus cohesion: Role for Rap1 GTPase and its exchange factor, PDZ-GEF in collective cell migration

Sawant, Ketki
http://rave.ohiolink.edu/etdc/view?acc_num=csu1449833763

Abstract Details

2015, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Cell movement is essential for the development and maintenance of complex multicellular organism. Excessive migration contributes to cancer metastasis and autoimmune diseases, whereas reduced migration can cause developmental defects and immunodeficiencies. In many biological process cells migrate in coordinate groups called “collectives”. Moreover, Collective cell migration is a now well established mode of metastasis in certain carcinomas. Despite the broad impact on normal development and disease, the molecular mechanisms that facilitate collective migration in vivo are still not well understood. We use border cell migration during Drosophila oogenesis as a genetically tractable model to study collective cell migration in the native three-dimensional environment of the tissue. During oogenesis, a pair of specialized cells, the polar cells, signal to recruit 6-8 cells follicular epithelial cells to form the border cell cluster. The cluster is composed of migratory border cells and the non-migratory pair of polar cells. The cluster then detaches from the follicular epithelium and migrates as a cohesive cluster from the anterior to posterior end of the egg chamber. The mechanism that controls detachment and migration as cohesive group are still poorly understood. Presence of cell – cell adhesion is a defining characteristic of collectively migrating cells, including border cells. The regulation of E-cadherin, cell adhesion molecule, is complex in migrating border cells, because E-cadherin forms differential but robust adhesions during migration. In this thesis, I investigated role of two proteins PDZ-GEF and its target Rap1 GTPase in collective border cell migration. We discovered that both of these proteins were required for collective cell migration. Loss of Rap1 and PDZ-GEF cause disorganization of E-cadherin protein localization at border cell-border cell and border cell-nurse cell junctions, resulting in migration failure. In contrast, hyperactivation of Rap1 caused more stable adhesions to be formed between border cell cluster and the follicular epithelial membrane, thus preventing cluster detachment. Therefore Rap1 GTPase spatially controls E-cadherin during border cell migration. However, further investigation is required to understand the molecular mechanism for how Rap1 controls E-cadherin stability still needs to be studied.
Jocelyn McDonald, PhD (Advisor)
Aaron Severson, PhD (Committee Member)
Michelle Longworth, PhD (Committee Member)
Jun Qin, PhD (Committee Member)
120 p.
Biology; Cellular Biology; Genetics; Molecular Biology
Cell migration, Collective cell migration, Border cell migration, Rap1 GTPase, PDZ-GEF

Recommended Citations

Citations

  • Sawant, K. (2015). Detachment versus cohesion: Role for Rap1 GTPase and its exchange factor, PDZ-GEF in collective cell migration [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1449833763

    APA Style (7th edition)

  • Sawant, Ketki. Detachment versus cohesion: Role for Rap1 GTPase and its exchange factor, PDZ-GEF in collective cell migration . 2015. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1449833763.

    MLA Style (8th edition)

  • Sawant, Ketki. "Detachment versus cohesion: Role for Rap1 GTPase and its exchange factor, PDZ-GEF in collective cell migration ." Doctoral dissertation, Cleveland State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=csu1449833763

    Chicago Manual of Style (17th edition)

csu1449833763
372
© 2015, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.