Accumulating evidence underscores the T-cell immune synapse (IS) as a site of intense vesicular trafficking, on which productive signaling and cell activation crucially depend. Although the T-cell antigen receptor (TCR) is known to exploit recycling to accumulate to the IS, the specific pathway that controls this process remains to be elucidated. Here we demonstrate that the small GTPase Rab29 is centrally implicated in TCR trafficking and IS assembly. Rab29 colocalized and interacted with Rab8, Rab11 and IFT20, a component of the intraflagellar transport system that regulates ciliogenesis and participates in TCR recycling in the non-ciliated T cell, as assessed by co-immunoprecipitation and immunofluorescence analysis. Rab29 depletion resulted in the inability of TCRs to undergo recycling to the IS, thereby compromizing IS assembly. Under these conditions, recycling TCRs accumulated in Rab11(+) endosomes that failed to polarize to the IS due to defective Rab29-dependent recruitment of the dynein microtubule motor. Remarkably, Rab29 participates in a similar pathway in ciliated cells to promote primary cilium growth and ciliary localization of Smoothened. These results provide a function for Rab29 as a regulator of receptor recycling and identify this GTPase as a shared participant in IS and primary cilium assembly.

Onnis, A., Finetti, F., Patrussi, L., Gottardo, M., Cassioli, C., Spanò, S., et al. (2015). The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis. CELL DEATH AND DIFFERENTIATION, 22(10), 1687-1699 [10.1038/cdd.2015.17].

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Onnis, Anna;Finetti, Francesca;Patrussi, Laura;Gottardo, Marco;Cassioli, Chiara;Baldari, Cosima
2015-01-01

Abstract

Accumulating evidence underscores the T-cell immune synapse (IS) as a site of intense vesicular trafficking, on which productive signaling and cell activation crucially depend. Although the T-cell antigen receptor (TCR) is known to exploit recycling to accumulate to the IS, the specific pathway that controls this process remains to be elucidated. Here we demonstrate that the small GTPase Rab29 is centrally implicated in TCR trafficking and IS assembly. Rab29 colocalized and interacted with Rab8, Rab11 and IFT20, a component of the intraflagellar transport system that regulates ciliogenesis and participates in TCR recycling in the non-ciliated T cell, as assessed by co-immunoprecipitation and immunofluorescence analysis. Rab29 depletion resulted in the inability of TCRs to undergo recycling to the IS, thereby compromizing IS assembly. Under these conditions, recycling TCRs accumulated in Rab11(+) endosomes that failed to polarize to the IS due to defective Rab29-dependent recruitment of the dynein microtubule motor. Remarkably, Rab29 participates in a similar pathway in ciliated cells to promote primary cilium growth and ciliary localization of Smoothened. These results provide a function for Rab29 as a regulator of receptor recycling and identify this GTPase as a shared participant in IS and primary cilium assembly.
Onnis, A., Finetti, F., Patrussi, L., Gottardo, M., Cassioli, C., Spanò, S., et al. (2015). The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis. CELL DEATH AND DIFFERENTIATION, 22(10), 1687-1699 [10.1038/cdd.2015.17].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/982777