Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

Larsen, Jørgen Hannover; Jensen, Martin Borch; Bhatia, Vikram; Pedersen, Sven; Bjørnholm, Thomas; Iversen, Lars; Uline, Mark J.; Szleifer, Igal; Jensen, Knud J.; Hatzakis, Nikos S.; Stamou, Dimitrios

doi:10.1038/nchembio.1733

Cited by 110 publications

(163 citation statements)

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“…Whether this ubiquitylation triggers membrane endocytosis and recycling remains to be investigated, but it has been suggested that CAR proteins might be involved in this process. Membrane curvature has also been shown to be essential for the generation of membrane raft-like liquid ordered phases and, in turn, for the localization of lipid-anchored proteins (37). Interestingly, CAR proteins, among other ABA signaling components, might be localized on membrane nanodomains (38).…”

Section: +mentioning

confidence: 99%

“…These structures provide a curved discontinuity at the cell membrane that functions as a platform for signaling proteins, as the presence of a bulkier lipid polar head leads to a reduction in the lateral energy barrier required for the insertion of hydrophobic protein segments and/or lipidated proteins (Fig. 8) (37). It is known that the membrane specificity of these proteins relies not only on the unambiguous binding to a particular lipid polar head but also on the recognition of intrinsically curved membrane architecture; furthermore, it has been demonstrated that protein membrane recognition will be more efficient if the membrane curvature is similar to that induced by the protein (33,58).…”

Section: +mentioning

confidence: 99%

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Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

Díaz

Sánchez-Barrena

González-Rubio

et al. 2015

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

110

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Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca 2+ are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca 2+ signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca 2+ -dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca 2+ sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca 2+ -dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress.signaling | ion transport | membrane biology | abiotic stress M any of the plant-adaptive responses to environmental stresses occur at the cell membrane. In particular, those related to the regulation of plant ion transporters as stress unbalance cell ion homeostasis (1, 2). The phytohormone abcisic acid (ABA) and the second messenger Ca 2+ have central roles in regulating plant stress tolerance through the control of the activity of various families of protein kinases and phosphatases that regulate the activation of different ion channels or transporters (3-7). Given the presence of the channel substrates at the cell membranes and the transient nature of their activation, the functioning of these systems relies on the regulated localization of different molecular entities in the vicinity of the channels via protein-protein (8, 9) and/or protein-membrane interactions (10, 11).The pyrabactin resistance 1/PYR1-like (PYR/PYL)/regulatory components of ABA receptors (RCAR) receptors perceive intracellular ABA levels and, as a result, form ternary complexes with clade A protein phosphatases type 2C (PP2C), thereby inactivating them (12)(13)(14)(15). This prevents the PP2C-mediated dephosphorylation of ABA-activated sucrose nonfermenting 1-related protein kinases (SnRKs) subfamily 2 (SnRK2s), which results in the activation of an SnRK2-dependent phosphorylation cascade affecting a high number of targets in the plant cell (16,17). As a result, ABA-activated SnRK2s are key players in regulating...

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Section: +mentioning

confidence: 99%

Section: +mentioning

confidence: 99%

Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

Díaz

Sánchez-Barrena

González-Rubio

et al. 2015

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

110

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“…Members of the Ras superfamily are posttranslationally modified at the carboxy-terminal end by prenylated and acylated lipid anchors, which are tethered to the inner cytosolic leaflet of the plasma membrane (31). Studies of surface-bound lipid-modified Ras peptides containing two saturated palmitoyl and one unsaturated farnesyl lipids have shown that such structures preferentially partitioned at raft microdomain boundaries (32,33), causing perturbations such as membrane thinning by displacing lipid headgroups (34).…”

Section: The Molecular Mechanism Of Signal Transduction Induced By Thmentioning

confidence: 99%

The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B

Cohen

2016

Antimicrob Agents Chemother

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Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB-induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells.

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“…6 Intriguingly, the acyl group of a palmitoylated protein prefers to insert into curved rather than planar membranes, because it is easier for the acyl chain to penetrate between phospholipid head groups. 7 This implies that palmitoylated proteins will naturally cluster in invaginated (curved) lipid-ordered domains (such as those that form during endocytosis). The ordering of membrane proteins with bulky cytoplasmic domains, such as the Na pump and NCX, would further promote the development of curvature.…”

Section: S-palmitoylation and The Regulation Of Cardiac Na Transportersmentioning

confidence: 99%

S-palmitoylation and the regulation of NCX1

2015

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Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

Cited by 110 publications

References 35 publications

Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B

S-palmitoylation and the regulation of NCX1

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