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Drosophila Subdued is a moonlighting transmembrane protein 16 (TMEM16) that transports ions and phospholipids.

Publication ,  Journal Article
Le, T; Le, SC; Yang, H
Published in: J Biol Chem
March 22, 2019

Transmembrane protein 16 (TMEM16) family members play numerous important physiological roles, ranging from controlling membrane excitability and secretion to mediating blood coagulation and viral infection. These diverse functions are largely due to their distinct biophysical properties. Mammalian TMEM16A and TMEM16B are Ca2+-activated Cl- channels (CaCCs), whereas mammalian TMEM16F, fungal afTMEM16, and nhTMEM16 are moonlighting (multifunctional) proteins with both Ca2+-activated phospholipid scramblase (CaPLSase) and Ca2+-activated, nonselective ion channel (CAN) activities. To further understand the biological functions of the enigmatic TMEM16 proteins in different organisms, here, by combining an improved annexin V-based CaPLSase-imaging assay with inside-out patch clamp technique, we thoroughly characterized Subdued, a Drosophila TMEM16 ortholog. We show that Subdued is also a moonlighting transport protein with both CAN and CaPLSase activities. Using a TMEM16F-deficient HEK293T cell line to avoid strong interference from endogenous CaPLSases, our functional characterization and mutagenesis studies revealed that Subdued is a bona fide CaPLSase. Our finding that Subdued is a moonlighting TMEM16 expands our understanding of the molecular mechanisms of TMEM16 proteins and their evolution and physiology in both Drosophila and humans.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

March 22, 2019

Volume

294

Issue

12

Start / End Page

4529 / 4537

Location

United States

Related Subject Headings

  • Phospholipids
  • Phospholipid Transfer Proteins
  • Permeability
  • Ion Transport
  • Humans
  • HEK293 Cells
  • Gene Knockdown Techniques
  • Drosophila Proteins
  • Drosophila
  • Cations
 

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Le, T., Le, S. C., & Yang, H. (2019). Drosophila Subdued is a moonlighting transmembrane protein 16 (TMEM16) that transports ions and phospholipids. J Biol Chem, 294(12), 4529–4537. https://doi.org/10.1074/jbc.AC118.006530
Le, Trieu, Son C. Le, and Huanghe Yang. “Drosophila Subdued is a moonlighting transmembrane protein 16 (TMEM16) that transports ions and phospholipids.J Biol Chem 294, no. 12 (March 22, 2019): 4529–37. https://doi.org/10.1074/jbc.AC118.006530.
Le, Trieu, et al. “Drosophila Subdued is a moonlighting transmembrane protein 16 (TMEM16) that transports ions and phospholipids.J Biol Chem, vol. 294, no. 12, Mar. 2019, pp. 4529–37. Pubmed, doi:10.1074/jbc.AC118.006530.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

March 22, 2019

Volume

294

Issue

12

Start / End Page

4529 / 4537

Location

United States

Related Subject Headings

  • Phospholipids
  • Phospholipid Transfer Proteins
  • Permeability
  • Ion Transport
  • Humans
  • HEK293 Cells
  • Gene Knockdown Techniques
  • Drosophila Proteins
  • Drosophila
  • Cations