title: Addressing the Functional Determinants of FAK during Ciliogenesis in Multiciliated Cells.
abstract: We previously identified focal adhesion kinase (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 down-regulation 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 amino-terminal (FERM) and carboxyl-terminal (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 with its role at FAs.
authors.affiliation: From the Laboratory of Cell Biology and Molecular Embryology, Department of Biological Sciences, University of Cyprus, 1 University Avenue, Nicosia 2109, Cyprus.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Antoniades
authors.affiliation: From the Laboratory of Cell Biology and Molecular Embryology, Department of Biological Sciences, University of Cyprus, 1 University Avenue, Nicosia 2109, Cyprus.
authors.forename: Panayiota
authors.initials: P
authors.lastname: Stylianou
authors.affiliation: From the Laboratory of Cell Biology and Molecular Embryology, Department of Biological Sciences, University of Cyprus, 1 University Avenue, Nicosia 2109, Cyprus.
authors.forename: Neophytos
authors.initials: N
authors.lastname: Christodoulou
authors.affiliation: From the Laboratory of Cell Biology and Molecular Embryology, Department of Biological Sciences, University of Cyprus, 1 University Avenue, Nicosia 2109, Cyprus skourip@ucy.ac.cy.
authors.forename: Paris A
authors.initials: PA
authors.lastname: Skourides
mesh_terms: D008841:Actin Cytoskeleton / Q000201:enzymology / Q000235:genetics; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D064652:Basal Bodies / Q000201:enzymology*; D002645:Chickens; D002923:Cilia / Q000201:enzymology / Q000235:genetics; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D030161:Avian Proteins; C496060:PXN protein, Xenopus; D051419:Paxillin; D029867:Xenopus Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: PTK2 protein tyrosine kinase 2 (PTK2) (focal adhesion kinase) (FAK); Xenopus; cell biology; cilia; ciliary adhesions; focal adhesions; motile cilia; paxillin