Flotillins promote T cell receptor sorting through a fast Rab5–Rab11 endocytic recycling axis

Gregory M. I. Redpath, Manuela Ecker, Natasha Kapoor-Kaushik, Haig Vartoukian, Michael Carnell, Daryan Kempe, Maté Biro, Nicholas Ariotti and Jérémie Rossy ()
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Gregory M. I. Redpath: University of New South Wales
Manuela Ecker: University of New South Wales
Natasha Kapoor-Kaushik: University of New South Wales
Haig Vartoukian: University of New South Wales
Michael Carnell: University of New South Wales
Daryan Kempe: University of New South Wales
Maté Biro: University of New South Wales
Nicholas Ariotti: University of New South Wales
Jérémie Rossy: University of New South Wales

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract The targeted endocytic recycling of the T cell receptor (TCR) to the immunological synapse is essential for T cell activation. Despite this, the mechanisms that underlie the sorting of internalised receptors into recycling endosomes remain poorly understood. To build a comprehensive picture of TCR recycling during T cell activation, we developed a suite of new imaging and quantification tools centred on photoactivation of fluorescent proteins. We show that the membrane-organising proteins, flotillin-1 and -2, are required for TCR to reach Rab5-positive endosomes immediately after endocytosis and for transfer from Rab5- to Rab11a-positive compartments. We further observe that after sorting into in Rab11a-positive vesicles, TCR recycles to the plasma membrane independent of flotillin expression. Our data suggest a mechanism whereby flotillins delineate a fast Rab5-Rab11a endocytic recycling axis and functionally contribute to regulate the spatial organisation of these endosomes.

Date: 2019
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DOI: 10.1038/s41467-019-12352-w

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