Ciliary protein CEP290 regulates focal adhesion via microtubule system in non-ciliated cells¹

Almost all differentiated mammalian cells have primary cilia on their surface. Ciliary dysfunction causes ciliopathy in humans. Centrosomal protein 290 (CEP290) is a ciliary protein that causes ciliopathies, localizes at the cilial base in ciliated cells, whereas it localizes to the centrosome in non-ciliated proliferating cells. The cilia-dependent function of CEP290 has been extensively studied; however, the cilia-independent function, which is likely responsible for the wider phenotypic spectra of CEP290-related ciliopathies, remains largely unknown. Here, we examined cilia-independent functions of CEP290 in non-ciliated cells. Our study showed thatCep290function loss suppresses microtubule elongation due to microtubule organizing center malfunction. Surprisingly, CEP290 forms a complex with the adenomatous polyposis coli (APC) protein encoded by theadenomatous polyposis coligene. The APC-CEP290 complex exists in the centrosome and on microtubule fibers. Notably, the reduced focal adhesion formation is likely responsible for theCep290mutant phenotypes, including impaired directed cell migration, shrunken cell shape, and reduced adhesive capacity to the extracellular matrix. The APC-CEP290 complex is consistently important for transporting a focal adhesion molecule, paxillin, to focal adhesions in non-ciliated cells. Thus, our findings provide a novel platform to better understand the ciliopathies.