Rab8 in TCR recycling

T-cell activation is initiated through the engagement of a T-cell receptor (TCR) with the cognate peptide–major-histocompatibility complex of an antigen-presenting cell, forming the so-called immune synapse. Sustained signalling at the immune synapse is required for T-cell maturation and is achieved by the steady recruitment of new TCRs as engaged receptors undergo internalisation. Cosima Baldari and colleagues have previously shown that IFT20, a component of the intraflagellar transport (IFT) system that is crucial for ciliogenesis, is involved in the regulation of TCR recycling. In their work on page 2541, they now investigate the role of the small GTPase Rab8, which has been implicated in ciliary trafficking, at the immune synapse. The authors show here that Rab8 controls polarised TCR recycling downstream of IFT20 by recruiting the vesicular (v)-SNARE VAMP-3, which promotes the final steps of delivery of receptor cargo from recycling endosomes to the plasma membrane. Interestingly, Rab8 also participates in IFT20-independent recycling pathways in T-cells, as exemplified by its role in chemokine receptor CXCR4 recycling. Taken together, the data presented here suggest that Rab8 and IFT20 act in concert in the regulation of TCR recycling, with IFT20 being involved at an early step and Rab8, through VAMP-3, at a later step in the pathway. Moreover, these results also emphasise the remarkable conservation in the pathways that orchestrate immune synapse formation and ciliogenesis.