TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking.
Sci Rep
; 9(1): 619, 2019 01 24.
Article
em En
| MEDLINE
| ID: mdl-30679690
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
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Cálcio
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Proteínas de Transferência de Fosfolipídeos
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Receptor de Morte Celular Programada 1
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Anoctaminas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article