The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Identification of a lipid scrambling domain in ANO6/TMEM16F
Open accessAbstract
Phospholipid scrambling (PLS) is a ubiquitous cellular mechanism involving the regulated bidirectional transport of phospholipids down their concentration gradient between membrane leaflets. ANO6/TMEM16F has been shown to be essential for Ca2+-dependent PLS, but controversy surrounds whether ANO6 is a phospholipid scramblase or an ion channel like other ANO/TMEM16 family members. Combining patch clamp recording with measurement of PLS, we show that ANO6 elicits robust Ca2+-dependent PLS coinciding with ionic currents that are explained by ionic leak during phospholipid translocation. By analyzing ANO1-ANO6 chimeric proteins, we identify a domain in ANO6 necessary for PLS and sufficient to confer this function on ANO1, which normally does not scramble. Homology modeling shows that the scramblase domain forms an unusual hydrophilic cleft that faces the lipid bilayer and may function to facilitate translocation of phospholipid between membrane leaflets. These findings provide a mechanistic framework for understanding PLS and how ANO6 functions in this process.
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Cites
Lipid landscapes and pipelines in membrane homeostasis
Holthuis, J. C. M., & Menon, A. K. (2014) · Nature · doi:10.1038/nature13474 · Cited by 901
PIP 2 Is a Necessary Cofactor for Ion Channel Function: How and Why?
Suh, B.-C., & Hille, B. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125859 · Cited by 646
Molecular mediators of macrophage fusion
Helming, L., & Gordon, S. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.07.005 · Cited by 326
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Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane
Bevers, E. M., & Williamson, P. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00020.2015 · Cited by 447
Cryo-EM structures of the TMEM16A calcium-activated chloride channel
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Janks, L., Sprague, R. S., & Egan, T. M. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801101 · Cited by 45
Metadata
- Authors
- Yu, K., Whitlock, J. M., Lee, K., Ortlund, E. A., Yuan Cui, Y., & Hartzell, H. C.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-06-09
- Volume
- 4
- Pages
- e06901-e06901
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W1868383480
- Cited by
- 179
- References
- 3
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yu, K., Whitlock, J. M., Lee, K., Ortlund, E. A., Yuan Cui, Y., & Hartzell, H. C. (2015). Identification of a lipid scrambling domain in ANO6/TMEM16F. eLife. https://doi.org/10.7554/elife.06901
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