Role of myosin VA in the cytoplasm-nucleus shuttling of focal adhesion kinase (FAK)

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is crucial for the regulation of distinct cellular functions, such as cell migration and proliferation. In addition to its canonical roles in integrin and growth factor receptors-mediated cytoplasmic signaling, recent studies have revealed the molecular mechanisms regulated by FAK in the nucleus. In the nuclear compartment FAK can interact with transcription factors and regulate processes such as survival, inflammation, differentiation and cell growth. However, the mechanisms of the cytoplasmic-nucleus transport of FAK remain poorly understood. Recent results (article in preparation) have demonstrated that FAK interacts physically with myosin Va in vitro and that these proteins are co-localized in the focal adhesions and nucleus of fibroblasts, however, it is unclear whether myosin Va transports FAK to the nuclear compartment. In this project we will carried out experiments based on photonics in order to investigate whether FAK is transported by myosin Va to the nucleus. Functional experiments will also be performed to clarify the importance of myosin Va for the nuclear localization of this kinase. The findings of this project should allow us to demonstrate how the focal adhesion kinase is transported to the nucleus, the subcellular region where this kinase works to regulate cellular homeostasis and the pathogenesis of several diseases, such as cancer, pulmonary fibrosis, hypertrophy and heart failure.