Hydrophobic mismatch sorts SNARE proteins into distinct membrane domains

Milovanović, Dragomir; Honigmann, Alf; Koike, Seiichi; Göttfert, Fabian; Pähler, Gesa; Junius, Meike; Müllar, Stefan; Diederichsen, Ulf; Janshoff, Andreas; Grubmüller, Helmut; Risselada, Herre Jelger; Eggeling, Christian; Hell, Stefan W.; Bogaart, Geert van den; Jahn, Reinhard

doi:10.1038/ncomms6984

Cited by 146 publications

(154 citation statements)

References 70 publications

(121 reference statements)

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“…A mismatch between the length of the transmembrane domain and the lipid bilayer can also induce the clustering of Sx1A (ref. 26). Single-molecule imaging analysis of Sx1A expressed in spinal cord neurons revealed that Sx1A mobility is more restricted at synapses when compared with extrasynaptic sites2728.…”

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confidence: 99%

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

et al. 2016

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Syntaxin1A is organized in nanoclusters that are critical for the docking and priming of secretory vesicles from neurosecretory cells. Whether and how these nanoclusters are affected by neurotransmitter release in nerve terminals from a living organism is unknown. Here we imaged photoconvertible syntaxin1A-mEos2 in the motor nerve terminal of Drosophila larvae by single-particle tracking photoactivation localization microscopy. Opto- and thermo-genetic neuronal stimulation increased syntaxin1A-mEos2 mobility, and reduced the size and molecular density of nanoclusters, suggesting an activity-dependent release of syntaxin1A from the confinement of nanoclusters. Syntaxin1A mobility was increased by mutating its polyphosphoinositide-binding site or preventing SNARE complex assembly via co-expression of tetanus toxin light chain. In contrast, syntaxin1A mobility was reduced by preventing SNARE complex disassembly. Our data demonstrate that polyphosphoinositide favours syntaxin1A trapping, and show that SNARE complex disassembly leads to syntaxin1A dissociation from nanoclusters. Lateral diffusion and trapping of syntaxin1A in nanoclusters therefore dynamically regulate neurotransmitter release.

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confidence: 99%

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

et al. 2016

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“…The neuronal plasma membrane SNARE syntaxin-1a may be more soluble in Ld than in Lo phase membranes (Bacia et al, 2004) because of different lipid ordering (Murray and Tamm, 2009) or because of hydrophobic mismatch (Milovanovic et al, 2015). Interestingly, the cholesterol-dependent clustering of syntaxin-1a is further modulated by electrostatic interactions with negatively charged lipids including phosphatidylserine (PS) and phosphatidylinositol-(4,5)-bisphosphate (PIP 2 ) (Murray and Tamm, 2009, 2011; van den Bogaart and Jahn, 2011).…”

Section: Effect Of Cholesterol On Snare-mediated Intracellular Membramentioning

confidence: 99%

The role of cholesterol in membrane fusion

Yang

Kreutzberger

Lee

et al. 2016

Chemistry and Physics of Lipids

325

269

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Cholesterol modulates the bilayer structure of biological membranes in multiple ways. It changes the fluidity, thickness, compressibility, water penetration and intrinsic curvature of lipid bilayers. In multi-component lipid mixtures, cholesterol induces phase separations, partitions selectively between different coexisting lipid phases, and causes integral membrane proteins to respond by changing conformation or redistribution in the membrane. But, which of these often overlapping properties are important for membrane fusion? – Here we review a range of recent experiments that elucidate the multiple roles that cholesterol plays in SNARE-mediated and viral envelope glycoprotein-mediated membrane fusion.

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“…Briefly, membrane curvature necessary for vesicular formation is facilitated by hydrophobic mismatch as results of protein crowding, as well as scaffolding mechanisms with the aid of coat proteins [36*]. Hydrophobic mismatch causes proteins, which have large extramembrane components diffusing in the membrane, to induce molecular crowding in order to lower the accessible membrane surface area and reduced lipids [37].…”

Section: Interplay Between Lipids and Proteins In Vesicular Formationmentioning

confidence: 99%

Membrane lipids and cell signaling

Sunshine

Iruela‐Arispe

2017

Current Opinion in Lipidology

195

132

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Purpose of review Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last three years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction. Recent findings In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers. Recent reports have also shown that the degree of saturation of phospholipids can reduce the activation of certain G-protein coupled receptors, as well as signaling downstream to Toll-like receptor 4 with consequences to NFkB activation and inflammation. Levels of specific gangliosides in the membrane were reported to activate integrins in a cell-autonomous manner affecting tumor cell migration. Furthermore, high resolution of the association of cholesterol with the Smoothened receptor has clarified its participation in sonic hedgehog signaling. These are some of the key advancements that have further propelled our understanding of the broad versatile contributions of membrane lipids in signal transduction. Summary As we gain definitive detail regarding the impact of lipid-protein interactions and their consequences to cell function, the options for therapeutic targeting expand with the possibility of greater specificity.

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Hydrophobic mismatch sorts SNARE proteins into distinct membrane domains

Cited by 146 publications

References 70 publications

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

The role of cholesterol in membrane fusion

Membrane lipids and cell signaling

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