CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium.

The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear.

IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases.

Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown.

The proteome speciation of an immortalized cystic fibrosis cell line: New perspectives on the pathophysiology of the disease.

Unlabelled: Cystic Fibrosis (CF) is a recessively inherited disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR has a pivotal role in the onset of CF, and several proteins are involved in its homeostasis. To study CFTR interactors at protein species level, we used a functional proteomics approach combining 2D-DIGE, mass spectrometry and enrichment analysis.

Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity.

Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog.

Centrosome amplification in CHO and DT40 cells by inactivation of cyclin-dependent kinases.

To study the mechanism of centrosome duplication in cycling cells, we established a novel system of multiple centrosome formation in two types of cells: CHO cells treated with RO3306, a Cyclin-dependent kinase 1 (Cdk1) inhibitor and DT40 cells, in which Cdks were knocked out by chemical genetics. Cdk1-inactivated cells initiated DNA replication and centrosome duplication at the onset of S phase. They became arrested at the end of G2, but the centrosome cycle continued to produce supernumerary centrioles/centrosomes without DNA endoreplication in those cells.