Ciliary protein CEP290 regulates focal adhesion via microtubule system in non-ciliated cells 1
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (Arcadia Science)
- @AvasthiReading's saved articles (AvasthiReading)
Abstract
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 that Cep290 function loss suppresses microtubule elongation due to microtubule organizing center malfunction. Surprisingly, CEP290 forms a complex with the adenomatous polyposis coli (APC) protein encoded by the adenomatous polyposis coli gene. The APC-CEP290 complex exists in the centrosome and on microtubule fibers. Notably, the reduced focal adhesion formation is likely responsible for the Cep290 mutant 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.
Article activity feed
-
This is an incredibly interesting and novel result identifying a role for the CEP290 ciliary transition zone protein in cytoplasmic microtubule dynamics and adhesion. One immediate question given the work is done in IMCD3 cells that are competent to form cilia is whether there is expression and a role for CEP290 in cells that are not, such as Jurkat T cells that express many ciliary proteins for use in the immunological synapse but never form a cilium. Those are suspension cells so the adhesion phenotypes may not be evident, but given the more generalized role in microtubule dynamics shown here, I wonder whether CEP290 is expressed in this cell type, when during the cell cycle it might be expressed in a cilium-incompetent cell type such as this, and if there are phenotypes associated in its knockdown in such a context. The last …
This is an incredibly interesting and novel result identifying a role for the CEP290 ciliary transition zone protein in cytoplasmic microtubule dynamics and adhesion. One immediate question given the work is done in IMCD3 cells that are competent to form cilia is whether there is expression and a role for CEP290 in cells that are not, such as Jurkat T cells that express many ciliary proteins for use in the immunological synapse but never form a cilium. Those are suspension cells so the adhesion phenotypes may not be evident, but given the more generalized role in microtubule dynamics shown here, I wonder whether CEP290 is expressed in this cell type, when during the cell cycle it might be expressed in a cilium-incompetent cell type such as this, and if there are phenotypes associated in its knockdown in such a context. The last certainly is out of scope of the current work but perhaps existing publicly available datasets would contain the information about expression and cell cycle-associated (and therefore microtubule reorganization associated) timing of CEP290 expression in truly cilium-independent context.
-
This is an incredibly interesting and novel result identifying a role for the CEP290 ciliary transition zone protein in cytoplasmic microtubule dynamics and adhesion. One immediate question given the work is done in IMCD3 cells that are competent to form cilia is whether there is expression and a role for CEP290 in cells that are not, such as Jurkat T cells that express many ciliary proteins for use in the immunological synapse but never form a cilium. Those are suspension cells so the adhesion phenotypes may not be evident, but given the more generalized role in microtubule dynamics shown here, I wonder whether CEP290 is expressed in this cell type, when during the cell cycle it might be expressed in a cilium-incompetent cell type such as this, and if there are phenotypes associated in its knockdown in such a context. The last …
This is an incredibly interesting and novel result identifying a role for the CEP290 ciliary transition zone protein in cytoplasmic microtubule dynamics and adhesion. One immediate question given the work is done in IMCD3 cells that are competent to form cilia is whether there is expression and a role for CEP290 in cells that are not, such as Jurkat T cells that express many ciliary proteins for use in the immunological synapse but never form a cilium. Those are suspension cells so the adhesion phenotypes may not be evident, but given the more generalized role in microtubule dynamics shown here, I wonder whether CEP290 is expressed in this cell type, when during the cell cycle it might be expressed in a cilium-incompetent cell type such as this, and if there are phenotypes associated in its knockdown in such a context. The last certainly is out of scope of the current work but perhaps existing publicly available datasets would contain the information about expression and cell cycle-associated (and therefore microtubule reorganization associated) timing of CEP290 expression in truly cilium-independent context.
-
