Indexed on: 29 Nov '16Published on: 28 Nov '16Published in: Journal of Biological Chemistry
We have previously identified FAK as an important regulator of ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins associate with the basal bodies and their striated rootlets and form complexes named ciliary adhesions (CAs). CAs display similarities with FAs but are established in an integrin independent fashion and are responsible for anchoring basal bodies to the actin cytoskeleton during ciliogenesis, as well as in mature multiciliated cells. FAK downregulation leads to aberrant ciliogenesis due to impaired association between the basal bodies and the actin cytoskeleton, suggesting that FAK is an important regulator of the CA complex. However, the mechanism through which FAK functions in the complex is not clear and in this study we examined the role of this protein in both ciliogenesis and ciliary function. We show that localization of FAK at CAs depends on interactions taking place at the FERM and the FAT domains and that both domains are required for proper ciliogenesis and ciliary function. Furthermore we show that an interaction with another CA protein, paxillin, is essential for correct localization of FAK in multiciliated cells. This interaction is indispensable for both ciliogenesis and ciliary function. Finally we provide evidence that despite the fact that FAK is in the active, open conformation at CAs, its kinase activity is dispensable for ciliogenesis and ciliary function revealing that FAK plays a scaffolding role in multiciliated cells. Overall these data show that the role of FAK at CAs displays similarities but also important differences compared to its role at FAs.