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 journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number619
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Cell-Derived Microparticles
Ionophores
Cell Membrane
Membranes
T-Lymphocytes
Jurkat Cells
Phosphatidylserines
Platelet Activation
Blood Coagulation
Eukaryotic Cells
T-Cell Antigen Receptor
Endocytosis
Ion Channels
Osteogenesis
Microscopy
Phospholipids

ASJC Scopus subject areas

  • General

Cite this

TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking. / Bricogne, Christopher; Fine, Michael; Pereira, Pedro M.; Sung, Julia; Tijani, Maha; Wang, Youxue; Henriques, Ricardo; Collins, Mary K.; Hilgemann, Donald.

In: Scientific Reports, Vol. 9, No. 1, 619, 01.12.2019.

Research output: Contribution to journalArticle

Bricogne, Christopher ; Fine, Michael ; Pereira, Pedro M. ; Sung, Julia ; Tijani, Maha ; Wang, Youxue ; Henriques, Ricardo ; Collins, Mary K. ; Hilgemann, Donald. / TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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AU - Wang, Youxue

AU - Henriques, Ricardo

AU - Collins, Mary K.

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