Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. Lina Dagnino

Abstract

Integrin-linked kinase (ILK) is a widely expressed scaffold protein important for cell adhesion, migration, and phagocytosis. ILK and its interacting partner, engulfment and cell motility protein 2 (ELMO2), may also modulate microtubule dynamics. Here, I show that sustained microtubule growth and acetylated tubulin levels are reduced in the absence of ILK and, conversely, that exogenous ILK exerts a stabilizing effect on microtubules. Further, exogenous ELMO2, ras homology growth related protein (RHOG) and ras-related C3 botulinum toxin substrate 1 (RAC1) stabilize microtubules in an ILK-dependent manner. Potential downstream effectors of the effect of ILK on microtubule stability include glycogen synthase kinase- 3 beta (GSK-3β), collapsin response mediator protein 2 (CRMP2) and stathmin 1 (STMN1). Taken together, my results provide evidence for a novel RHOG/ILK/ELMO2-RAC1 pathway in differentiated keratinocytes that likely promotes microtubule stabilization via CRMP2 activation and STMN1 inactivation.


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