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

Christopher Bricogne, Michael Fine, Pedro M. Pereira, Julia Sung, Maha Tijani, Youxue Wang, Ricardo Henriques, Mary K. Collins, Donald Hilgemann

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Article number619
JournalScientific reports
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General


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