Abstract
Ciliated cells exploit a specific transport system, the intraflagellar transport (IFT) system, to ensure the traffic of molecules from the cell body to the cilium. However, it is now clear that IFT activity is not restricted to cilia-related functions. This is strikingly exemplified by the observation that IFT proteins play important roles in cells lacking a primary cilium, such as lymphocytes. Indeed, in T cells the IFT system regulates the polarized transport of endosome-associated T cell antigen receptors and signaling mediators during assembly of the immune synapse, a specialized interface that forms on encounter with a cognate antigen presenting cell and on which T cell activation and effector function crucially depend. Cellular degradation pathways have recently emerged as new extraciliary functions of the IFT system. IFT proteins have been demonstrated to regulate autophagy in ciliated cells through their ability to recruit the autophagy machinery to the base of the cilium. We have now implicated the IFT component IFT20 in another central degradation process that also controls the latest steps in autophagy, namely lysosome function, by regulating the cation-independent mannose-6-phosphate receptor (CI-MPR)-dependent lysosomal targeting of acid hydrolases. This involves the ability of IFT20 to act as an adaptor coupling the CI-MPR to dynein for retrograde transport to the trans-Golgi network. In this short review we will discuss the emerging roles of IFT proteins in cellular degradation pathways.
Highlights
Primary cilium assembly and function crucially relies on the intraflagellar transport (IFT) system
We showed that IFT20 acts in concert with other IFT proteins to promote the assembly of the T cell immune synapse (Finetti et al, 2009), a specialized signaling platform that forms when a T cell encounters an antigen presenting cell that displays a specific peptide ligand bound to MHC and on which T cell activation crucially depends (Dustin and Choudhuri, 2016)
We have previously reported that T cell activation and differentiation are impaired in T cells lacking IFT20 both in vitro and in vivo in a T cell-specific conditional knockout mouse and showed that this results from its ability to promote the polarized recycling to the immune synapse of endosome-associated TCR and LAT (Finetti et al, 2009; Vivar et al, 2016)
Summary
Primary cilium assembly and function crucially relies on the intraflagellar transport (IFT) system. This function involves the ability of IFT20 to interface with trafficking regulators and molecular motors to allow for the polarized delivery to the synaptic membrane of T cell antigen receptors and membrane-bound signaling mediators associated with recycling endosomes (Finetti et al, 2014; Onnis et al, 2016; Vivar et al, 2016; Figure 1B).
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