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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Bricogne C,Fine M,Pereira PM,Sung J,Tijani M,Wang Y,Henriques R,Collins MK,Hilgemann DWdoi
10.1038/s41598-018-37056-xsubject
Has Abstractpub_date
2019-01-24 00:00:00pages
619issue
1issn
2045-2322pii
10.1038/s41598-018-37056-xjournal_volume
9pub_type
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