TMEM16F and dynamins control expansive plasma membrane reservoirs
| Autor: | Ruhma Syeda, Donald W. Hilgemann, Christine Deisl, Michael Fine |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Dynamins
Cytoplasm Phospholipid scramblase Science Anoctamins General Physics and Astronomy Membrane trafficking Small GTPases Article Exocytosis General Biochemistry Genetics and Molecular Biology Gene Knockout Techniques Phospholipid scrambling Humans Cell migration Phospholipid Transfer Proteins Phospholipids Dynamin Membranes Multidisciplinary Chemistry Cell Membrane General Chemistry Endocytosis Basal plasma membrane HEK293 Cells Membrane Biophysics Calcium Mechanosensitive channels |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Cells can expand their plasma membrane laterally by unfolding membrane undulations and by exocytosis. Here, we describe a third mechanism involving invaginations held shut by the membrane adapter, dynamin. Compartments open when Ca activates the lipid scramblase, TMEM16F, anionic phospholipids escape from the cytoplasmic monolayer in exchange for neutral lipids, and dynamins relax. Deletion of TMEM16F or dynamins blocks expansion, with loss of dynamin expression generating a maximally expanded basal plasma membrane state. Re-expression of dynamin2 or its GTPase-inactivated mutant, but not a lipid binding mutant, regenerates reserve compartments and rescues expansion. Dynamin2-GFP fusion proteins form punctae that rapidly dissipate from these compartments during TMEM16F activation. Newly exposed compartments extend deeply into the cytoplasm, lack numerous organellar markers, and remain closure-competent for many seconds. Without Ca, compartments open slowly when dynamins are sequestered by cytoplasmic dynamin antibodies or when scrambling is mimicked by neutralizing anionic phospholipids and supplementing neutral lipids. Activation of Ca-permeable mechanosensitive channels via cell swelling or channel agonists opens the compartments in parallel with phospholipid scrambling. Thus, dynamins and TMEM16F control large plasma membrane reserves that open in response to lateral membrane stress and Ca influx. Cells locally expand and retract their surface in response to environmental factors such as changes in membrane tension. Here the authors show the membrane adapter, dynamin2, locally constricts surface membrane to form an isolated but contiguous membrane reservoir that can open upon phospholipid scrambling via TMEM16F. |
| Databáze: | OpenAIRE |
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