The Ran importin system in cilia trafficking.

Cilia are microtubule-based organelles that arise from the centrosome and project from the surface of many cells. Defects in cilia-localized proteins are felt to lead to polycystic kidney disease as well as ciliopathies with multiple organ involvement. Movement of proteins along mammalian cilia is a specialized process that is highly related to the intraflagellar movement of proteins in lower organisms. Entry of proteins into the cilia appears to be a tightly regulated process. Several cilia-targeting sequences have been identified that appear to mediate the movement of proteins into cilia, although the molecular basis through which these sequences operate is still being elucidated. Entry of proteins into cilia appears to be regulated at the base of the cilia at a region known as the transition zone. It has been proposed that a ciliary pore exists in this zone that controls entry of proteins into the cilia, similar to the nuclear pore that controls entry of proteins into the nucleus. Our group at the University of Michigan has found that proteins important in nuclear import appear to function similarly in cilia entry. In particular, we have identified roles for the small GTPase, Ran and its binding partners, the importins, in regulating cilia entry of specific proteins.