Regulation of β1 Integrin Traffic and ARF6 Gtpase by Amp-Activated Protein Kinase
thesisposted on 22.05.2021, 11:45 authored by Rehman Ata
Integrins are cell surface receptors that physically bridge the extracellular matrix to the cytoskeleton and responsible for adhesion, migration, and signaling. Integrin function is intimately controlled by their membrane traffic. For example, integrins are dynamically internalized from the cell posterior and recycled to the cell anterior during cell migration. Misregulation of integrins is intimately linked with cancer progression, including metastasis and cell proliferation and survival. We have recently uncovered that integrin membrane traffic is controlled by AMP-activated protein kinase (AMPK), an energy stress sensing kinase within cells at becomes activated upon energy stress such as by an increase in cell AMP:ATP ratio. I confirmed that AMPK activation resulted in a reduction of cell surface β1-integrin. Using assays that selectively measure integrin exocytosis and endocytosis, I found that AMPK activation regulates β1-integrin recycling and possibly endocytosis. I demonstrated that AMPK regulates Arf6 localization, a key protein which regulates β1-integrin membrane traffic. I confirmed that Arf6 and clathrin are involved in reciprocal regulation, thus highlighting the possible pathway for β1-integrin regulation by AMPK.