Cell polarity

Most vertebrate cells have a primary cilium that extends up to 10 μm outwards from the cell as a single, nonmotile appendage. This structure consists of a specialized ciliary membrane that surrounds a microtubule-based structure termed the axoneme. The ciliary membrane is biochemically distinct from, yet continuous with, the plasma membrane. Primary cilia sense a diverse range of environmental signals in the extracellular milieu, and through various surface receptors localized on the ciliary membrane, relay these signals to the cell body. Primary cilia act as photosensors (rhodopsin signaling in cone and rod photoreceptors), chemosensors (odorant receptors on olfactory neurons), mechanosensors (e.g., signaling in response to urine flow in the kidney), and biochemical sensors (e.g., signaling by growth factors receptors). Important signaling pathways involved in cell proliferation, differentiation, survival and migration such as Hedgehog (Hh), Wnt, Notch, Hippo and PDFG-a signaling are orchestrated in the primary cilium. Given the importance of its role, it is not surprising that primary cilium dysfunction is associated with a large list of heterogeneous human developmental and degenerative disorders, collectively known as ciliopathies, that affect nearly every major body organ.

We are interested in the analysis of the participation of members of the MAL protein family in primary cilium formation. Previous results indicate that plasmolipin (PLLP), a member of the MAL family, is required for primary ciliogenesis in polarized epithelial cells. We have recently carried out a proteomic analysis of the proteins pulled-down with PLLP. Among the proteins identified we found several subunits of different tethering factors of the Complex Associated with Tethering Containing Helical Rods (CATCHR) family. The project to be carrying out will deal with the characterization of the interaction of PLLP, with the CATCHR tethering factor GARP/EARP complexes and the study of their role in primary ciliogenesis.