A continuum membrane model can predict curvature sensing by helix insertion

Cell shape is well described by membrane curvature. Septins are filament-forming, GTP-binding proteins that assemble on positive, micrometer-scale curvatures. Here, we examine the molecular basis of curvature sensing by septins. We show that differences in affinity and the number of binding sites drive curvature-specific adsorption of septins. Moreover, we find septin assembly onto curved membranes is cooperative and show that geometry influences higher-order arrangement of septin filaments. Although septins must form polymers to stay associated with membranes, septin filaments do not have to span micrometers in length to sense curvature, as we find that single-septin complexes have curvature-dependent association rates. We trace this ability to an amphipathic helix (AH) located on the C-terminus of Cdc12. The AH domain is necessary and sufficient for curvature sensing both in vitro and in vivo. These data show that curvature sensing by septins operates at much smaller length scales than the micrometer curvatures being detected.

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Membrane Curvature Sensing by Amphipathic Helices

Journal of Biological Chemistry ◽

10.1074/jbc.m111.271130 ◽

2011 ◽

Vol 286 (49) ◽

pp. 42603-42614 ◽

Cited By ~ 77

Author(s):

Martin Borch Jensen ◽

Vikram Kjøller Bhatia ◽

Christine C. Jao ◽

Jakob Ewald Rasmussen ◽

Søren L. Pedersen ◽

...

Keyword(s):

Membrane Curvature ◽

Curvature Sensing ◽

Amphipathic Helices

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How curved membranes recruit amphipathic helices and protein anchoring motifs

Nature Chemical Biology ◽

10.1038/nchembio.213 ◽

2009 ◽

Vol 5 (11) ◽

pp. 835-841 ◽

Cited By ~ 247

Author(s):

Nikos S Hatzakis ◽

Vikram K Bhatia ◽

Jannik Larsen ◽

Kenneth L Madsen ◽

Pierre-Yves Bolinger ◽

...

Keyword(s):

Amphipathic Helices ◽

Curved Membranes

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A time course of orchestrated endophilin action in sensing, bending, and stabilizing curved membranes

Molecular Biology of the Cell ◽

10.1091/mbc.e16-04-0264 ◽

2016 ◽

Vol 27 (13) ◽

pp. 2119-2132 ◽

Cited By ~ 10

Author(s):

Kumud R. Poudel ◽

Yongming Dong ◽

Hang Yu ◽

Allen Su ◽

Thuong Ho ◽

...

Keyword(s):

Lipid Bilayers ◽

Time Course ◽

Synaptic Activity ◽

Amphipathic Helices ◽

Membrane Compartments ◽

Bending Mechanism ◽

Membrane Changes ◽

Curved Membranes

Numerous proteins act in concert to sculpt membrane compartments for cell signaling and metabolism. These proteins may act as curvature sensors, membrane benders, and scaffolding molecules. Here we show that endophilin, a critical protein for rapid endocytosis, quickly transforms from a curvature sensor into an active bender upon membrane association. We find that local membrane deformation does not occur until endophilin inserts its amphipathic helices into lipid bilayers, supporting an active bending mechanism through wedging. Our time-course studies show that endophilin continues to drive membrane changes on a seconds-to-minutes time scale, indicating that the duration of endocytosis events constrains the mode of endophilin action. Finally, we find a requirement of coordinated activities between wedging and scaffolding for endophilin to produce stable membrane tubules in vitro and to promote synaptic activity in vivo. Together these data demonstrate that endophilin is a multifaceted molecule that precisely integrates activities of sensing, bending, and stabilizing curvature to sculpt membranes with speed.

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Structural basis for the geometry-driven localization of a small protein

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1423868112 ◽

2015 ◽

Vol 112 (15) ◽

pp. E1908-E1915 ◽

Cited By ~ 45

Author(s):

Richard L. Gill ◽

Jean-Philippe Castaing ◽

Jen Hsin ◽

Irene S. Tan ◽

Xingsheng Wang ◽

...

Keyword(s):

Lipid Bilayers ◽

Structural Basis ◽

Supported Lipid Bilayers ◽

Curvature Sensing ◽

Preferential Localization ◽

Acyl Chains ◽

Shape Sensing ◽

Α Helix ◽

Dynamics Simulations ◽

Curved Membranes

In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVMP9A) to reveal that SpoVM’s atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM’s membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.

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Correction: A continuum membrane model can predict curvature sensing by helix insertion

Soft Matter ◽

10.1039/d1sm90225c ◽

2022 ◽

Author(s):

Yiben Fu ◽

Wade F. Zeno ◽

Jeanne C. Stachowiak ◽

Margaret E. Johnson

Keyword(s):

Soft Matter ◽

Membrane Model ◽

Curvature Sensing

Correction for ‘A continuum membrane model can predict curvature sensing by helix insertion’ by Yiben Fu et al., Soft Matter, 2021, 17, 10649–10663, DOI: 10.1039/D1SM01333E.

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Membrane Curvature Sensing by Amphipathic Helices: Insights from Implicit Membrane Modeling

Biophysical Journal ◽

10.1016/j.bpj.2018.03.030 ◽

2018 ◽

Vol 114 (9) ◽

pp. 2128-2141 ◽

Cited By ~ 13

Author(s):

Binod Nepal ◽

John Leveritt ◽

Themis Lazaridis

Keyword(s):

Membrane Curvature ◽

Curvature Sensing ◽

Amphipathic Helices ◽

Membrane Modeling

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Dynamic mechanochemical feedback between curved membranes and BAR protein self-organization

Nature Communications ◽

10.1038/s41467-021-26591-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Anabel-Lise Le Roux ◽

Caterina Tozzi ◽

Nikhil Walani ◽

Xarxa Quiroga ◽

Dobryna Zalvidea ◽

...

Keyword(s):

Molecular Organization ◽

Self Organization ◽

Membrane Mechanics ◽

Curvature Sensing ◽

Cellular Processes ◽

Mechanical Responses ◽

Curved Membranes ◽

Comprehensive Framework ◽

Membrane Shape ◽

Template Size

AbstractIn many physiological situations, BAR proteins reshape membranes with pre-existing curvature (templates), contributing to essential cellular processes. However, the mechanism and the biological implications of this reshaping process remain unclear. Here we show, both experimentally and through modelling, that BAR proteins reshape low curvature membrane templates through a mechanochemical phase transition. This phenomenon depends on initial template shape and involves the co-existence and progressive transition between distinct local states in terms of molecular organization (protein arrangement and density) and membrane shape (template size and spherical versus cylindrical curvature). Further, we demonstrate in cells that this phenomenon enables a mechanotransduction mode, in which cellular stretch leads to the mechanical formation of membrane templates, which are then reshaped into tubules by BAR proteins. Our results demonstrate the interplay between membrane mechanics and BAR protein molecular organization, integrating curvature sensing and generation in a comprehensive framework with implications for cell mechanical responses.

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Interdisciplinary Synergy to Reveal Mechanisms of Annexin-Mediated Plasma Membrane Shaping and Repair

Cells ◽

10.3390/cells9041029 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1029 ◽

Cited By ~ 2

Author(s):

Poul Martin Bendix ◽

Adam Cohen Simonsen ◽

Christoffer D. Florentsen ◽

Swantje Christin Häger ◽

Anna Mularski ◽

...

Keyword(s):

Plasma Membrane ◽

Cell Biology ◽

Membrane Damage ◽

Membrane Integrity ◽

Interdisciplinary Approach ◽

Membrane Repair ◽

Cell Membrane Integrity ◽

Curvature Sensing ◽

Plasma Membrane Repair ◽

Curved Membranes

The plasma membrane surrounds every single cell and essentially shapes cell life by separating the interior from the external environment. Thus, maintenance of cell membrane integrity is essential to prevent death caused by disruption of the plasma membrane. To counteract plasma membrane injuries, eukaryotic cells have developed efficient repair tools that depend on Ca2+- and phospholipid-binding annexin proteins. Upon membrane damage, annexin family members are activated by a Ca2+ influx, enabling them to quickly bind at the damaged membrane and facilitate wound healing. Our recent studies, based on interdisciplinary research synergy across molecular cell biology, experimental membrane physics, and computational simulations show that annexins have additional biophysical functions in the repair response besides enabling membrane fusion. Annexins possess different membrane-shaping properties, allowing for a tailored response that involves rapid bending, constriction, and fusion of membrane edges for resealing. Moreover, some annexins have high affinity for highly curved membranes that appear at free edges near rupture sites, a property that might accelerate their recruitment for rapid repair. Here, we discuss the mechanisms of annexin-mediated membrane shaping and curvature sensing in the light of our interdisciplinary approach to study plasma membrane repair.

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Regulation of LC3 lipidation by the autophagy-specific class III phosphatidylinositol-3 kinase complex

Molecular Biology of the Cell ◽

10.1091/mbc.e18-11-0743 ◽

2019 ◽

Vol 30 (9) ◽

pp. 1098-1107 ◽

Cited By ~ 14

Author(s):

Livia W. Brier ◽

Liang Ge ◽

Goran Stjepanovic ◽

Ashley M. Thelen ◽

James H. Hurley ◽

...

Keyword(s):

Membrane Curvature ◽

Specific Class ◽

Class Iii ◽

Interacting Protein ◽

Curvature Sensing ◽

A Cell ◽

The Alps ◽

Curved Membranes ◽

Phosphatidylinositol 3

Autophagy is a conserved eukaryotic pathway critical for cellular adaptation to changes in nutrition levels and stress. The class III phosphatidylinositol (PI)3-kinase complexes I and II (PI3KC3-C1 and -C2) are essential for autophagosome initiation and maturation, respectively, from highly curved vesicles. We used a cell-free reaction that reproduces a key autophagy initiation step, LC3 lipidation, as a biochemical readout to probe the role of autophagy-related gene (ATG)14, a PI3KC3-C1-specific subunit implicated in targeting the complex to autophagy initiation sites. We reconstituted LC3 lipidation with recombinant PI3KC3-C1, -C2, or various mutant derivatives added to extracts derived from a CRISPR/Cas9-generated ATG14-knockout cell line. Both complexes C1 and C2 require the C-terminal helix of VPS34 for activity on highly curved membranes. However, only complex C1 supports LC3 lipidation through the curvature-targeting amphipathic lipid packing sensor (ALPS) motif of ATG14. Furthermore, the ALPS motif and VPS34 catalytic activity are required for downstream recruitment of WD-repeat domain phosphoinositide-interacting protein (WIPI)2, a protein that binds phosphatidylinositol 3-phosphate and its product phosphatidylinositol 3, 5-bisphosphate, and a WIPI-binding protein, ATG2A, but do not affect membrane association of ATG3 and ATG16L1, enzymes contributing directly to LC3 lipidation. These data reveal the nuanced role of the ATG14 ALPS in membrane curvature sensing, suggesting that the ALPS has additional roles in supporting LC3 lipidation.

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