Membrane re-modelling by BAR domain superfamily proteins via molecular and non-molecular factors

Lipid membranes are structural components of cell surfaces and intracellular organelles. Alterations in lipid membrane shape are accompanied by numerous cellular functions, including endocytosis, intracellular transport, and cell migration. Proteins containing Bin–Amphiphysin–Rvs (BAR) domains (BAR proteins) are unique, because their structures correspond to the membrane curvature, that is, the shape of the lipid membrane. BAR proteins present at high concentration determine the shape of the membrane, because BAR domain oligomers function as scaffolds that mould the membrane. BAR proteins co-operate with various molecular and non-molecular factors. The molecular factors include cytoskeletal proteins such as the regulators of actin filaments and the membrane scission protein dynamin. Lipid composition, including saturated or unsaturated fatty acid tails of phospholipids, also affects the ability of BAR proteins to mould the membrane. Non-molecular factors include the external physical forces applied to the membrane, such as tension and friction. In this mini-review, we will discuss how the BAR proteins orchestrate membrane dynamics together with various molecular and non-molecular factors.

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Curvature induction and sensing of the F-BAR protein Pacsin1 on lipid membranes via molecular dynamics simulations

Scientific Reports ◽

10.1038/s41598-019-51202-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Md. Iqbal Mahmood ◽

Hiroshi Noguchi ◽

Kei-ichi Okazaki

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Lipid Membranes ◽

Lipid Membrane ◽

Complex Structure ◽

Membrane Curvature ◽

Coarse Grained ◽

Lateral Interaction ◽

Bar Domain ◽

Dynamics Simulations

Abstract F-Bin/Amphiphysin/Rvs (F-BAR) domain proteins play essential roles in biological processes that involve membrane remodelling, such as endocytosis and exocytosis. It has been shown that such proteins transform the lipid membrane into tubes. Notably, Pacsin1 from the Pacsin/Syndapin subfamily has the ability to transform the membrane into various morphologies: striated tubes, featureless wide and thin tubes, and pearling vesicles. The molecular mechanism of this interesting ability remains elusive. In this study, we performed all-atom (AA) and coarse-grained (CG) molecular dynamics simulations to investigate the curvature induction and sensing mechanisms of Pacsin1 on a membrane. From AA simulations, we show that Pacsin1 has internal structural flexibility. In CG simulations with parameters tuned from the AA simulations, spontaneous assembly of two Pacsin1 dimers through lateral interaction is observed. Based on the complex structure, we show that the regularly assembled Pacsin1 dimers bend a tensionless membrane. We also show that a single Pacsin1 dimer senses the membrane curvature, binding to a buckled membrane with a preferred curvature. These results provide molecular insights into polymorphic membrane remodelling.

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Feedback between membrane tension, lipid shape and curvature in the formation of packing defects

10.1101/389627 ◽

2018 ◽

Cited By ~ 2

Author(s):

M. Pinot ◽

S. Vanni ◽

E. Ambroggio ◽

D. Guet ◽

B. Goud ◽

...

Keyword(s):

Intracellular Transport ◽

Lipid Membrane ◽

Membrane Curvature ◽

Membrane Tension ◽

Membrane Pore ◽

Membrane Deformation ◽

Lipid Packing ◽

Head Groups ◽

Packing Defects ◽

The Alps

AbstractLipid packing defects favor the binding of proteins to cellular membranes by creating spaces between lipid head groups that allow the insertion of amphipathic helices or lipid modifications. The density of packing defects in a lipid membrane is well known to increase with membrane curvature and in the presence of conical-shaped lipids. In contrast, the role of membrane tension in the formation of lipid packing defects has been poorly investigated. Here we use a combination of numerical simulations and experiments to measure the effect of membrane tension on the density of lipid packing defects. We first monitor the binding of ALPS (amphipathic lipid packing sensor) to giant unilamellar vesicles and observe a striking periodic binding of ALPS that we attribute to osmotically-induced membrane tension and transient membrane pore formation. Using micropipette aspiration experiments, we show that a high membrane tension induces a reversible increase in the density of lipid packing defects. We next focus on packing defects induced by lipid shape and show that conical lipids generate packing defects similar to that induced by membrane tension and enhance membrane deformation due to the insertion of the ALPS helix. Both cyclic ALPS binding and the cooperative effect of ALPS binding and conical lipids on membrane deformation result from an interplay between helix insertion and lipid packing defects created by membrane tension, conical lipids and/or membrane curvature. We propose that feedback mechanisms involving membrane tension, lipid shape and membrane curvature play a crucial role in membrane deformation and intracellular transport events.

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Curvature-sensitive trans-assembly of human Atg8-family proteins in autophagy-related membrane tethering

10.1101/870857 ◽

2019 ◽

Cited By ~ 1

Author(s):

Saki Taniguchi ◽

Masayuki Toyoshima ◽

Tomoyo Takamatsu ◽

Joji Mima

Keyword(s):

Lipid Membranes ◽

De Novo ◽

Membrane Curvature ◽

Membrane Dynamics ◽

Membrane Structures ◽

Autophagosome Formation ◽

Molar Ratios ◽

Membrane Tethering ◽

Membrane Attachment

In macroautophagy, de novo formation of the double membrane-bound organelles, termed autophagosomes, is essential for engulfing and sequestering the cytoplasmic contents to be degraded in the lytic compartments such as vacuoles and lysosomes. Atg8-family proteins have been known to be responsible for autophagosome formation via membrane tethering and fusion events of precursor membrane structures. Nevertheless, how Atg8 proteins act directly upon autophagosome formation still remains enigmatic. Here, to further gain molecular insights into Atg8-mediated autophagic membrane dynamics, we study the two representative human Atg8 orthologs, LC3B and GATE-16, by quantitatively evaluating their intrinsic potency to physically tether lipid membranes in a chemically defined reconstitution system using purified Atg8 proteins and synthetic liposomes. Both LC3B and GATE-16 retained the capacities to trigger efficient membrane tethering at the protein-to-lipid molar ratios ranging from 1:100 to 1:5,000. These human Atg8-mediated membrane tethering reactions require trans-assembly between the membrane-anchored forms of LC3B and GATE-16 and can be reversibly and strictly controlled by the membrane attachment and detachment cycles. Strikingly, we further uncovered distinct membrane curvature dependences of LC3B- and GATE-16-mediated membrane tethering reactions: LC3B can drive tethering more efficiently than GATE-16 for highly-curved small vesicles (e.g. 50 nm in diameter), although GATE-16 turns out to be a more potent tether than LC3B for flatter large vesicles (e.g. 200 and 400 nm in diameter). Our findings establish curvature-sensitive trans-assembly of human Atg8-family proteins in reconstituted membrane tethering, which recapitulates an essential subreaction of the biogenesis of autophagosomes in vivo.

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Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain–like mechanism

The Journal of Cell Biology ◽

10.1083/jcb.200609176 ◽

2007 ◽

Vol 176 (7) ◽

pp. 953-964 ◽

Cited By ~ 262

Author(s):

Pieta K. Mattila ◽

Anette Pykäläinen ◽

Juha Saarikangas ◽

Ville O. Paavilainen ◽

Helena Vihinen ◽

...

Keyword(s):

Mammalian Cells ◽

Membrane Curvature ◽

Membrane Dynamics ◽

Actin Dynamics ◽

Actin Binding ◽

Tubular Structures ◽

Membrane Deformation ◽

Bar Domain ◽

Membrane Protrusions ◽

Induce Plasma

The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P2-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P2-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin–bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis.

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Electrochemical Properties of Lipid Membranes Self-Assembled from Bicelles

Membranes ◽

10.3390/membranes11010011 ◽

2020 ◽

Vol 11 (1) ◽

pp. 11

Author(s):

Damian Dziubak ◽

Kamil Strzelak ◽

Slawomir Sek

Keyword(s):

Electrochemical Properties ◽

Self Assembly ◽

Lipid Membranes ◽

Lipid Membrane ◽

Membrane Resistance ◽

Electrochemical Characteristics ◽

Freeze Thaw ◽

Lipid Films ◽

Supported Lipid Membranes

Supported lipid membranes are widely used platforms which serve as simplified models of cell membranes. Among numerous methods used for preparation of planar lipid films, self-assembly of bicelles appears to be promising strategy. Therefore, in this paper we have examined the mechanism of formation and the electrochemical properties of lipid films deposited onto thioglucose-modified gold electrodes from bicellar mixtures. It was found that adsorption of the bicelles occurs by replacement of interfacial water and it leads to formation of a double bilayer structure on the electrode surface. The resulting lipid assembly contains numerous defects and pinholes which affect the permeability of the membrane for ions and water. Significant improvement in morphology and electrochemical characteristics is achieved upon freeze–thaw treatment of the deposited membrane. The lipid assembly is rearranged to single bilayer configuration with locally occurring patches of the second bilayer, and the number of pinholes is substantially decreased. Electrochemical characterization of the lipid membrane after freeze–thaw treatment demonstrated that its permeability for ions and water is significantly reduced, which was manifested by the relatively high value of the membrane resistance.

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Cardiolipin-Containing Lipid Membranes Attract the Bacterial Cell Division Protein DivIVA

International Journal of Molecular Sciences ◽

10.3390/ijms22158350 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8350

Author(s):

Naďa Labajová ◽

Natalia Baranova ◽

Miroslav Jurásek ◽

Robert Vácha ◽

Martin Loose ◽

...

Keyword(s):

Cell Division ◽

Lipid Bilayers ◽

Bacterial Cell ◽

Lipid Membranes ◽

Model Organism ◽

Active Role ◽

Membrane Curvature ◽

Bacterial Cell Division ◽

Division Site ◽

Clostridioides Difficile

DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane.

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Interactions of Lipid Droplets with the Intracellular Transport Machinery

International Journal of Molecular Sciences ◽

10.3390/ijms22052776 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2776

Author(s):

Selma Yilmaz Dejgaard ◽

John F. Presley

Keyword(s):

Membrane Trafficking ◽

Lipid Droplets ◽

Intracellular Transport ◽

Neutral Lipids ◽

Small Gtpases ◽

Lipid Phase ◽

Intracellular Organelles ◽

And Function ◽

Lipid Phase Separation ◽

Endocytic Pathways

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.

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Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes

Membranes ◽

10.3390/membranes11030192 ◽

2021 ◽

Vol 11 (3) ◽

pp. 192

Author(s):

Kinga Burdach ◽

Dagmara Tymecka ◽

Aneta Urban ◽

Robert Lasek ◽

Dariusz Bartosik ◽

...

Keyword(s):

Lipid Membranes ◽

Liquid Crystalline ◽

Lipid Membrane ◽

Attenuated Total Reflection ◽

Gram Positive ◽

Insertion Depth ◽

Force Microscopy ◽

Acyl Chains ◽

Hydrophobic Portion ◽

Membrane Fluidization

The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds.

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Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life ◽

10.3390/life11040332 ◽

2021 ◽

Vol 11 (4) ◽

pp. 332

Author(s):

Valentina Brillo ◽

Leonardo Chieregato ◽

Luigi Leanza ◽

Silvia Muccioli ◽

Roberto Costa

Keyword(s):

Molecular Mechanisms ◽

Mitochondrial Dynamics ◽

Eukaryotic Cells ◽

Therapeutic Approaches ◽

Cellular Functions ◽

Lipid Trafficking ◽

Mitochondrial Ros ◽

Intracellular Organelles ◽

Proliferation Regulation ◽

Dynamic Plasticity

Mitochondria are key intracellular organelles involved not only in the metabolic state of the cell, but also in several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these organelles are characterized by continuous events of fission and fusion which contribute to the dynamic plasticity of their network, also strongly influenced by mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount of reactive oxygen species (ROS) inside eukaryotic cells, which are reported to mediate a plethora of both physiological and pathological cellular functions, such as growth and proliferation, regulation of autophagy, apoptosis, and metastasis. Therefore, targeting mitochondrial ROS could be a promising strategy to overcome and hinder the development of diseases such as cancer, where malignant cells, possessing a higher amount of ROS with respect to healthy ones, could be specifically targeted by therapeutic treatments. In this review, we collected the ultimate findings on the blended interplay among mitochondrial shaping, mitochondrial ROS, and several signaling pathways, in order to contribute to the dissection of intracellular molecular mechanisms involved in the pathophysiology of eukaryotic cells, possibly improving future therapeutic approaches.

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