In or out of the groove? Mechanisms of lipid scrambling by TMEM16 proteins.

Autor: Feng Z; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States., Di Zanni E; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States., Alvarenga O; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States., Chakraborty S; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States., Rychlik N; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States; Institute of Physiology I, University of Münster, Robert-Koch-Str. 27a, D-48149 Münster, Germany., Accardi A; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States; Department of Biochemistry, Weill Cornell Medicine, New York, NY, United States. Electronic address: ala2022@med.cornell.edu.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2024 Jul; Vol. 121, pp. 102896. Date of Electronic Publication: 2024 May 09.
DOI: 10.1016/j.ceca.2024.102896
Abstrakt: Phospholipid scramblases mediate the rapid movement of lipids between membrane leaflets, a key step in establishing and maintaining membrane homeostasis of the membranes of all eukaryotic cells and their organelles. Thus, impairment of lipid scrambling can lead to a variety of pathologies. How scramblases catalyzed the transbilayer movement of lipids remains poorly understood. Despite the availability of direct structural information on three unrelated families of scramblases, the TMEM16s, the Xkrs, and ATG-9, a unifying mechanism has failed to emerge thus far. Among these, the most extensively studied and best understood are the Ca 2+ activated TMEM16s, which comprise ion channels and/or scramblases. Early work supported the view that these proteins provided a hydrophilic, membrane-exposed groove through which the lipid headgroups could permeate. However, structural, and functional experiments have since challenged this mechanism, leading to the proposal that the TMEM16s distort and thin the membrane near the groove to facilitate lipid scrambling. Here, we review our understanding of the structural and mechanistic underpinnings of lipid scrambling by the TMEM16s and discuss how the different proposals account for the various experimental observations.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessio Accardi reports financial support was provided by National Institutes of Health. Omar E. Alvarenga reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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