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TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking

Bricogne, C; Fine, M; Pereira, PM; Sung, J; Tijani, M; Wang, Y; Henriques, R; ... Hilgemann, DW; + view all (2019) TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking. Scientific Reports , 9 (1) , Article 619. 10.1038/s41598-018-37056-x. Green open access

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Abstract

TMEM16F is a Ca2+ -gated ion channel that is required for Ca2+ -activated phosphatidylserine exposure on the surface of many eukaryotic cells. TMEM16F is widely expressed and has roles in platelet activation during blood clotting, bone formation and T cell activation. By combining microscopy and patch clamp recording we demonstrate that activation of TMEM16F by Ca2+ ionophores in Jurkat T cells triggers large-scale surface membrane expansion in parallel with phospholipid scrambling. With continued ionophore application,TMEM16F-expressing cells then undergo extensive shedding of ectosomes. The T cell co-receptor PD-1 is selectively incorporated into ectosomes. This selectivity depends on its transmembrane sequence. Surprisingly, cells lacking TMEM16F not only fail to expand surface membrane in response to elevated cytoplasmic Ca2+, but instead undergo rapid massive endocytosis with PD-1 internalisation. These results establish a new role for TMEM16F as a regulator of Ca2+ activated membrane trafficking.

Type: Article
Title: TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-018-37056-x
Publisher version: https://doi.org/10.1038/s41598-018-37056-x
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. - With correction dated 17 May 2019.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10067749
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