Trafficking of proteins and lipids in primary cilia

Although largely considered a vestige before 1999, the primary cilium is now demonstrated as a signaling center to interpret both chemical and mechanical signals. Major components of multiple signaling pathways specifically localize in primary cilia. These include pathways that are essential for the biogenesis and homeostasis of tissues and organs, such as signaling mediated by Hedgehog, WNT, G protein-coupled receptors and growth factor receptors. Although continuously extended from the plasma membrane, the ciliary membrane possesses unique composition and compartmentalization of phosphoinositides.

PtdIns4P and PtdIns(4,5)P2 are the most well-studied ciliary phosphoinositides. PtdIns4P is the dominant phosphoinositide along the ciliary membrane; whereas, PtdIns(4,5)P2 is mainly limited to the proximal part of the cilium and the ciliary base. It has been suggested that the unique compartmentalization of phosphoinositide species, kinases and phosphatases in different sections of cilia is critical to regulate trafficking of signaling proteins into and out of cilia. In particular, phosphoinositide signaling plays an important role in the assembly and maintenance of the diffusion barrier at the base of cilia.

The lab's efforts focus on dissecting the phosphoinositide-dependent ciliary trafficking machinery using biochemistry and cell biological approaches, such as spatial interactome analysis and super-resolution microscopy.