RRC ID 67365
Author Suzuki J, Fujii T, Imao T, Ishihara K, Kuba H, Nagata S.
Title Calcium-dependent phospholipid scramblase activity of TMEM16 protein family members.
Journal J Biol Chem
Abstract BACKGROUND:TMEM16A and 16B work as Cl(-) channel, whereas 16F works as phospholipid scramblase. The function of other TMEM16 members is unknown.
RESULTS:Using TMEM16F(-/-) cells, TMEM16C, 16D, 16F, 16G, and 16J were shown to be lipid scramblases.
CONCLUSION:Some TMEM16 members are divided into two Cl(-) channels and five lipid scramblases.
SIGNIFICANCE:Learning the biochemical function ofTMEM16family members is essential to understand their physiological role. Asymmetrical distribution of phospholipids between the inner and outer plasma membrane leaflets is disrupted in various biological processes. We recently identified TMEM16F, an eight-transmembrane protein, as a Ca(2+)-dependent phospholipid scramblase that exposes phosphatidylserine (PS) to the cell surface. In this study, we established a mouse lymphocyte cell line with a floxed allele in the TMEM16F gene. When TMEM16F was deleted, these cells failed to expose PS in response to Ca(2+) ionophore, but PS exposure was elicited by Fas ligand treatment. We expressed other TMEM16 proteins in the TMEM16F(-/-) cells and found that not only TMEM16F, but also 16C, 16D, 16G, and 16J work as lipid scramblases with different preference to lipid substrates. On the other hand, a patch clamp analysis in 293T cells indicated that TMEM16A and 16B, but not other family members, acted as Ca(2+)-dependent Cl(-) channels. These results indicated that among 10 TMEM16 family members, 7 members could be divided into two subfamilies, Ca(2+)-dependent Cl(-) channels (16A and 16B) and Ca(2+)-dependent lipid scramblases (16C, 16D, 16F, 16G, and 16J).
Volume 288(19)
Pages 13305-16
Published 2013-5-10
DOI 10.1074/jbc.M113.457937
PII S0021-9258(19)54561-6
PMID 23532839
PMC PMC3650369
MeSH Animals Anoctamins Apoptosis Calcimycin / pharmacology Calcium Ionophores / pharmacology Calcium Signaling* Cell Line Cell Membrane / metabolism Chlorocebus aethiops Gene Expression Gene Knockout Techniques Humans Membrane Potentials Mice Molecular Sequence Annotation Organ Specificity Phosphatidylserines / metabolism Phospholipid Transfer Proteins / genetics* Phospholipid Transfer Proteins / metabolism fas Receptor / metabolism
IF 4.238
DNA material pMXs-puro-mTMEM16A (RDB18742) pMXs-puro-mTMEM16B (RDB18743) pMXs-puro-mTMEM16C (RDB18744) pMXs-puro-mTMEM16D (RDB18745) pMXs-puro-mTMEM16E (RDB18746) pMXs-puro-mTMEM16F (RDB18747) pMXs-puro-mTMEM16G (RDB18748) pMXs-puro-mTMEM16H (RDB18749) pMXs-puro-mTMEM16J (RDB18750) pMXs-puro-mTMEM16F-long (RDB18751) pMXs-puro-mTMEM16F-D409G (RDB18752) pMXs-puro-mTMEM16F-D409G long (RDB18753) pMXs-puro-mTMEM16F-R211L (RDB18754) pMXs-puro-mTMEM16F-D409G/R211L (RDB18755) pEF-mTMEM16A (RDB18756) pEF-mTMEM16B (RDB18757) pEF-mTMEM16C (RDB18758) pEF-mTMEM16D (RDB18759) pEF-mTMEM16E (RDB18760) pEF-mTMEM16F (RDB18761) pEF-mTMEM16G (RDB18762) pEF-mTMEM16H (RDB18763) pEF-mTMEM16J (RDB18764) pEF-mTMEM16K (RDB18765)