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Regulation of Talin-Mediated Integrin Activation

Holly, Ashley Elizabeth
http://rave.ohiolink.edu/etdc/view?acc_num=csu1456861275

Abstract Details

2016, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Talin is a critical cytoplasmic protein that triggers the conformational change and activation of integrins which mediate cell adhesion, spreading, and migration. This large cytoskeletal protein consists of an N-terminal FERM-domain containing head (TH) and a C-terminal 13-helical bundle rod. Without cellular stimulation, Talin is auto-inhibited through an N/C-terminal interaction where the integrin binding site in TH is masked by its own Talin rod. Conformational regulation, localization and activation of Talin via numerous pathways and mechanisms has been elusive for decades. This study focused on these issues by investigating three potential mechanisms: Mechanism 1: Structure-based functional study of an electrostatic “pull-push” mechanism for Talin activation. Mechanism 2: Structure-based functional elucidation of Talin recruitment to membrane by a novel interaction between TH and RAP1. Mechanism 3: NMR-based elucidation on membrane binding of Kindlin-3 via its N-terminus to cooperate with Talin for inducing potent integrin activation. Through these studies, I provide strong evidence that multiple regulatory mechanisms exist for Talin activation, recruitment and localization to promote integrin activation.
Jun Qin, PhD (Advisor)
Sadashiva Karnik, PhD (Committee Member)
Anton Komar, PhD (Committee Member)
Ed Plow, PhD (Committee Member)
Barsanjit Mazumder, PhD (Committee Member)
Aimin Zhou, PhD (Committee Member)
112 p.
Cellular Biology; Molecular Biology
Talin; Rap1; integrin; signaling; Kindlin

Recommended Citations

Citations

  • Holly, A. E. (2016). Regulation of Talin-Mediated Integrin Activation [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1456861275

    APA Style (7th edition)

  • Holly, Ashley. Regulation of Talin-Mediated Integrin Activation. 2016. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1456861275.

    MLA Style (8th edition)

  • Holly, Ashley. "Regulation of Talin-Mediated Integrin Activation." Doctoral dissertation, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1456861275

    Chicago Manual of Style (17th edition)

csu1456861275
606
© 2016, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.