Unknown

Dataset Information

0

Phospholipid scrambling induced by an ion channel/metabolite transporter complex.


ABSTRACT: Cells establish the asymmetrical distribution of phospholipids and alter their distribution by phospholipid scrambling (PLS) to adapt to environmental changes. Here, we demonstrate that a protein complex, consisting of the ion channel Tmem63b and the thiamine transporter Slc19a2, induces PLS upon calcium (Ca2+) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca2+ stimulation-mediated PLS is suppressed by deletion of Tmem63b, while human disease-related Tmem63b mutants induce constitutive PLS. To search for a molecular link between Ca2+ stimulation and PLS, we perform revival screening on Tmem63b-overexpressing cells, and identify Slc19a2 and the Ca2+-activated K+ channel Kcnn4 as PLS-regulating factors. Deletion of either of these genes decreases PLS activity. Biochemical screening indicates that Tmem63b and Slc19a2 form a heterodimer. These results demonstrate that a Tmem63b/Slc19a2 heterodimer induces PLS upon Ca2+ stimulation, along with Kcnn4 activation.

SUBMITTER: Niu H 

PROVIDER: S-EPMC11366033 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Phospholipid scrambling induced by an ion channel/metabolite transporter complex.

Niu Han H   Maruoka Masahiro M   Noguchi Yuki Y   Kosako Hidetaka H   Suzuki Jun J  

Nature communications 20240831 1


Cells establish the asymmetrical distribution of phospholipids and alter their distribution by phospholipid scrambling (PLS) to adapt to environmental changes. Here, we demonstrate that a protein complex, consisting of the ion channel Tmem63b and the thiamine transporter Slc19a2, induces PLS upon calcium (Ca<sup>2+</sup>) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca<sup>2+</sup> stimulation-mediated PLS is  ...[more]

Similar Datasets

| S-EPMC3970400 | biostudies-literature
| S-EPMC5003272 | biostudies-literature
| S-EPMC3668637 | biostudies-literature
| S-EPMC7668003 | biostudies-literature
| S-EPMC9521775 | biostudies-literature
| S-EPMC6478717 | biostudies-literature
| S-EPMC5866571 | biostudies-literature
| S-EPMC6684876 | biostudies-literature
| S-EPMC9299152 | biostudies-literature
| S-EPMC10874734 | biostudies-literature