INVESTIGATIONS ON THE ROLES OF RAB23 IN CILIARY TRANSPORT

Abstract

An exact role for small GTPase Rab23 has remained elusive. There have been several reports suggesting a ciliary-associated role for Rab23, however a direct correlation between the primary cilium and Rab23 is lacking. In this thesis, I show that Rab23 wild-type and constitutively active Rab23Q68L mutant are enriched at the primary cilia. Although Rab23 did not turn out to be critical in primary ciliogenesis; in testing the effect of Rab23¿s manipulations on the ciliary localization of several known ciliary cargoes, soluble kinesin-2 motor protein, Kif17¿s, ciliary enrichment was disrupted after overexpression of dominant negative Rab23S23N and Rab23 knockdown. Kif17 possibly requires regulatory proteins like Rab23 to facilitate binding to its putative import carrier, Importin ß2, for its ciliary transport. My findings have uncovered a hitherto unknown effector of Rab23, a potential ciliary transport role, and demonstrated how Rab23 could mediate Kif17¿s trafficking to the primary cilium.