Mechanisms shaping cell membranes

Kozlov, Michael M.; Campelo, Felix; Liska, Nicole; Chernomordik, Leonid V.; Marrink, Siewert J.; McMahon, Harvey T.

doi:10.1016/j.ceb.2014.03.006

Cited by 224 publications

(217 citation statements)

References 58 publications

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“…These two steps allow EHD2 to oligomerize when bound to the membranes, but not in solution. The energy that is necessary to deform the membrane is defined by the bending modulus (∼12 kcal/mol for a typical lipid bilayer) (30). It is interesting to note that this energy appears to be drawn from the association of EHD2 into membrane-bound oligomers and not from ATP hydrolysis.…”

Section: Discussionmentioning

confidence: 99%

EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation

Hoernke

Mohan

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The EH-domain-containing protein 2 (EHD2) is a dynamin-related ATPase that confines caveolae to the cell surface by restricting the scission and subsequent endocytosis of these membrane pits. For this, EHD2 is thought to first bind to the membrane, then to oligomerize, and finally to detach, in a stringently regulated mechanistic cycle. It is still unclear how ATP is used in this process and whether membrane binding is coupled to conformational changes in the protein. Here, we show that the regulatory N-terminal residues and the EH domain keep the EHD2 dimer in an autoinhibited conformation in solution. By significantly advancing the use of infrared reflection-absorption spectroscopy, we demonstrate that EHD2 adopts an open conformation by tilting the helical domains upon membrane binding. We show that ATP binding enables partial insertion of EHD2 into the membrane, where G-domain-mediated oligomerization occurs. ATP hydrolysis is related to detachment of EHD2 from the membrane. Finally, we demonstrate that the regulation of EHD2 oligomerization in a membrane-bound state is crucial to restrict caveolae dynamics in cells.EHD2 | caveolae | membrane-reshaping protein | membrane-bound protein structure | infrared reflection-absorption spectroscopy

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Section: Discussionmentioning

confidence: 99%

EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation

Hoernke

Mohan

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…These mechanisms might play a role in sorting receptors into (or excluding them from) membrane trafficking carriers. A high local concentration of proteins that bind to the membrane surface has been suggested to induce membrane curvature by a crowding mechanism (Stachowiak et al, 2012), although the contribution of this mechanism is still unclear (recently discussed in Kozlov et al, 2014).…”

Section: Partitioning Of Shaped Transmembrane Domains and Protein Cromentioning

confidence: 99%

Membrane curvature at a glance

McMahon

Boucrot

2015

Journal of Cell Science

621

589

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Membrane curvature is an important parameter in defining the morphology of cells, organelles and local membrane subdomains. Transport intermediates have simpler shapes, being either spheres or tubules. The generation and maintenance of curvature is of central importance for maintaining trafficking and cellular functions. It is possible that local shapes in complex membranes could help to define local subregions. In this Cell Science at a Glance article and accompanying poster, we summarize how generating, sensing and maintaining high local membrane curvature is an active process that is mediated and controlled by specialized proteins using general mechanisms: (i) changes in lipid composition and asymmetry, (ii) partitioning of shaped transmembrane domains of integral membrane proteins or protein or domain crowding, (iii) reversible insertion of hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the cytoskeleton with forces generated by polymerization and by molecular motors. We also summarize some of the discoveries about the functions of membrane curvature, where in addition to providing cell or organelle shape, local curvature can affect processes like membrane scission and fusion as well as protein concentration and enzyme activation on membranes.

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“…The beclin-1-interacting transmembrane ER Box 2. Principles for the generation of membrane curvature by protein action Generally, the modeling of cell membranes to yield curvature and to shape organelles, vesicles and tubules is thought to depend on several different principles (see box figure) (for recent reviews, see Derganc et al, 2013;Kirchhausen, 2012;Kozlov et al, 2014). An asymmetric distribution of membrane lipids causes membrane bending if the head groups on the two sides are of different sizes.…”

Section: Phagophore Nucleationmentioning

confidence: 99%

“…This type of process is referred to as membrane remodeling. The two types of shape transformations can collectively be termed membrane modeling (Campelo et al, 2010;Kozlov et al, 2014). Protein enrichment at high density on membrane surfaces membrane protein complex subunit 6 (EMC6) might further contribute to the generation of the unique geometry of the phagophore, as it localizes to omegasomes and its depletion causes the accumulation of autophagosomal precursor structures and impaired autophagy .…”

Section: Phagophore Nucleationmentioning

confidence: 99%

Membrane dynamics in autophagosome biogenesis

Carlsson

Simonsen

2015

Journal of Cell Science

186

169

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Bilayered phospholipid membranes are vital to the organization of the living cell. Based on fundamental principles of polarity, membranes create borders allowing defined spaces to be encapsulated. This compartmentalization is a prerequisite for the complex functional design of the eukaryotic cell, yielding localities that can differ in composition and operation. During macroautophagy, cytoplasmic components become enclosed by a growing double bilayered membrane, which upon closure creates a separate compartment, the autophagosome. The autophagosome is then primed for fusion with endosomal and lysosomal compartments, leading to degradation of the captured material. A large number of proteins have been found to be essential for autophagy, but little is known about the specific lipids that constitute the autophagic membranes and the membrane modeling events that are responsible for regulation of autophagosome shape and size. In this Commentary, we review the recent progress in our understanding of the membrane shaping and remodeling events that are required at different steps of the autophagy pathway.This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: 'ERES: sites for autophagosome biogenesis and maturation?' by Jana SanchezWandelmer et al. (J. Cell Sci. 128,(185)(186)(187)(188)(189)(190)(191)(192) and 'WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome' by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128,(207)(208)(209)(210)(211)(212)(213)(214)(215)(216)(217).

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Mechanisms shaping cell membranes

Cited by 224 publications

References 58 publications

EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation

EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation

Membrane curvature at a glance

Membrane dynamics in autophagosome biogenesis

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