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

Autor: Niu H; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyoku, Kyoto, Japan.; Graduate School of Biostudies, Kyoto University, Konoe-cho, Yoshida, Sakyoku, Kyoto, Japan., Maruoka M; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyoku, Kyoto, Japan.; Center for Integrated Biosystems, Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Noguchi Y; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyoku, Kyoto, Japan., Kosako H; Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan., Suzuki J; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyoku, Kyoto, Japan. jsuzuki@icems.kyoto-u.ac.jp.; Graduate School of Biostudies, Kyoto University, Konoe-cho, Yoshida, Sakyoku, Kyoto, Japan. jsuzuki@icems.kyoto-u.ac.jp.; Center for Integrated Biosystems, Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan. jsuzuki@icems.kyoto-u.ac.jp.; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. jsuzuki@icems.kyoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 31; Vol. 15 (1), pp. 7566. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1038/s41467-024-51939-w
Abstrakt: 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 2+ ) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca 2+ 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 Ca 2+ stimulation and PLS, we perform revival screening on Tmem63b-overexpressing cells, and identify Slc19a2 and the Ca 2+ -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 Ca 2+ stimulation, along with Kcnn4 activation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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