Dissecting the Vesicular Trafficking Function of IFT Subunits

Abstract

Intraflagellar transport (IFT) was initially identified as a transport machine with multiple protein subunits, and it is essential for the assembly, disassembly, and maintenance of cilium/flagellum, which serves as the nexus of extracellular-to-intracellular signal integration. To date, in addition to its well-established and indispensable roles in ciliated cells, most IFT subunits have presented more general functions of vesicular trafficking in the non-ciliated cells. Thus, this review aims to summarize the recent progress on the vesicular trafficking functions of the IFT subunits and to highlight the issues that may arise in future research.

Keywords: IFT; ciliopathy; cilium; flagellum; vesicular trafficking.

FIGURE 1

Vesicular trafficking function of IFT subunits in ciliated and non-ciliated cells. (A) In the ciliated cell, IFT20 localizes at both the cilium and the Golgi and transports the ciliary receptors from the Golgi to the cilium. Golgi resident protein GMAP210 recruits IFT20 at the Golgi. Another Golgi resident protein GM130, along with VPS15, regulates the release of IFT20-associated vesicles from the Golgi. IFT54 interacts with IFT20 and Rabaptin5, an effector of Rab8, to mediate the interaction of Rab8-Rabaptin5-containing and IFT20-containing vesicles when these vesicles are directed to the base of the cilium. At the basal body, these vesicles can be assembled with the other IFT subunits, and anterograde IFT trains transport ciliary receptors into the cilium. Some ciliary receptors could also be transported by recycling endosomes with the help of Rab8, Rab11, and BBSome. When the vesicles carrying Rab8, Rab11, and the BBSome reach the basal body, IFT25/27 interact with the BBSome to facilitate ciliary receptors incorporating into IFT trains. The BLOC-1 complex is also associated with the ciliary receptors in recycling endosome-derived vesicles. Moreover, IFT20 is partially responsible for the basal body localization of pallidin, one subunit of the BLOC-1 complex. Two components of the exocyst complex (Exo70 and Sec8) also interact with IFT20 at the basal body, which might facilitate the interaction of v-SNARE and t-SNARE. One component of DAPs, CCDC41, can recruit IFT20 to the basal body where several IFT subunits associated with vesicular trafficking are assembled into the whole IFT complex. (B) Vesicular trafficking functions of IFT20, IFT52, and IFT57 in the neuron. During the maturation of neurons, the microtubule organizing center (MTOC; centrosome) and Golgi are translocated toward the neurite. IFT20 localizes at the Golgi and transports synaptic vesicles along with IFT52 and IFT57 in polarized axons. (C) Vesicular trafficking functions of IFT subunits in T cells. When the T cell is activated, and the immune synapse (IS) begins to assemble, the (MTOC; centrosome) is translocated beneath the membrane domain of the IS. The Golgi and other vesicular compartments also relocate toward the IS. The T-cell receptors (TCRs) need to be transported to the IS for the activation of T cells. IFT20, localizing at the MTOC, Golgi, and endosomes, is required for polarized TCR recycling to the IS with the help of IFT52, IFT54, IFT57, and IFT88. Transmit of internalized TCRs from early endosomes (Rab5) to recycling endosomes (Rab4) or pericentrosomal recycling endosomes (Rab11) also needs IFT20. In addition, IFT20 also regulates the retrograde vesicular trafficking of the cation-independent mannose-6-phosphate receptors (CI-MPR) from lysosomes to the trans-Golgi network, thus controlling lysosome biogenesis in both ciliated and non-ciliated cells [only presented in (C)].