Lipid distribution and transport across cellular membranes

Pomorski, Thomas; Hrafnsdóttir, Sigrún; Devaux, Philippe F.; Meer, Gerrit van

doi:10.1006/scdb.2000.0231

Cited by 129 publications

(101 citation statements)

References 75 publications

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“…In turn, lipid transfer could be altered through the presence or conformational change of peptides (24) or translocase proteins (25,26), as has been observed for alamethicin and PS lipids (27). In Fig.…”

Section: Differences Between Planar Bilayers and Supported Bilayersmentioning

confidence: 78%

Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers

Collins

Keller²

2008

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

265

291

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Plasma membranes of cells are asymmetric in both lipid and protein composition. The mechanism by which proteins on both sides of the membrane colocalize during signaling events is unknown but may be due to the induction of inner leaflet domains by the outer leaflet. Here we show that liquid domains form in asymmetric Montal-Mueller planar bilayers in which one leaflet's composition would phase-separate in a symmetric bilayer and the other's would not. Equally important, by tuning the lipid composition of the second leaflet, we are able to suppress domains in the first leaflet. When domains are present in asymmetric membranes, each leaflet contains regions of three distinct lipid compositions, implying strong interleaflet interactions. Our results show that mechanisms of domain induction between the outer and inner leaflets of cell plasma membranes do not necessarily require the participation of membrane proteins. Based on these findings, we suggest mechanisms by which cells could actively regulate protein function by modulating local lipid composition or interleaflet interactions.cholesterol ͉ induction ͉ raft ͉ membrane ͉ phase C ell membranes are asymmetric in lipid composition between the inner and outer leaflet (1). Lipids of the two leaflets are assumed to also differ in their ability to separate into domains enriched in particular lipids and proteins. Model membranes composed with the goal to mimic the lipid mixture of the outer leaflet of a cell membrane separate into two liquid phases (2-4), whereas at least one inner leaflet mixture does not (5). To explain colocalization of inner and outer leaflet proteins during signaling events, it has been hypothesized that domains in the outer leaflet induce domains in the inner leaflet (6-8). However, domain induction across membrane leaflets is controversial. Some researchers argue that only proteins should be able to induce domains across leaflets (9). Other groups, including our own, have observed what seems to be domain induction across leaflets of protein-free membranes deposited on solid surfaces, but generally these efforts have been frustrated by experimental difficulties (7, 10-12).Here we construct asymmetric, protein-free, planar bilayers in water. One leaflet's composition would phase-separate in a symmetric bilayer and the other's would not. We show that liquid domains form in both leaflets of the asymmetric bilayer. One leaflet induces phase separation in the other. Equally important, we show that changing the lipid composition of the second leaflet suppresses domain formation in the original leaflet. We find that leaflets are strongly coupled. Our results imply that cells could tune membrane composition to create or annihilate domains. Because induction of domains occurs in planar membranes devoid of membrane proteins, induction of domains in cell membranes need not rely on membrane curvature or protein coupling (9,13,14).We construct membranes of diphytanoylphosphatidylcholine (DiPhyPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol (Chol)...

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Section: Differences Between Planar Bilayers and Supported Bilayersmentioning

confidence: 78%

Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers

Collins

Keller²

2008

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

265

291

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“…The cell membrane is asymmetric, with acidic phospholipids such as phosphatidylglycerol, phosphatidylserine, and phosphatidylinositol in the inner leaflet of the cell membrane (57). Extracellular stimuli induce the flipping of acidic phospholipids to the cell surface (58) where phosphatidylserine can be detected using fluorescently tagged recombinant annexin V (59).…”

Section: Discussionmentioning

confidence: 99%

The IL1α-S100A13 Heterotetrameric Complex Structure

Mohan

2011

Journal of Biological Chemistry

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Interleukin 1␣ (IL1␣) plays an important role in several key biological functions, such as angiogenesis, cell proliferation, and tumor growth in several types of cancer. IL1␣ is a potent cytokine that induces a wide spectrum of immunological and inflammatory activities. The biological effects of IL1␣ are mediated through the activation of transmembrane receptors (IL1Rs) and therefore require the release of the protein into the extracellular space. IL1␣ is exported through a non-classical release pathway involving the formation of a specific multiprotein complex, which includes IL1␣ and S100A13. Because IL1␣ plays an important role in cell proliferation and angiogenesis, inhibiting the formation of the IL1␣-S100A13 complex would be an effective strategy to inhibit a wide range of cancers. To understand the molecular events in the IL1␣ release pathway, we studied the structure of the IL1␣-S100A13 tetrameric complex, which is the key complex formed during the non-classical pathway of IL1␣ release.

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“…Their identities are maintained despite extensive interconnecting vesicular-trafficking pathways, and they require tight regulation of lipid sorting, metabolism, and transport (van Meer, 1993;Pomorski et al, 2001;van Meer and Sprong, 2004). Increasing lines of evidence suggest that lipid-transfer proteins (LTPs) play a major role in regulating the lipid composition of membranous organelles (Sprong et al, 2001;De Matteis et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

Peretti

Dahan

Shimoni

et al. 2008

MBoC

290

272

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Lipid transport between intracellular organelles is mediated by vesicular and nonvesicular transport mechanisms and is critical for maintaining the identities of different cellular membranes. Nonvesicular lipid transport between the endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the lipid composition of the Golgi membranes. Here, we show that the integral ER-membrane proteins VAP-A and VAP-B affect the structural and functional integrity of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the Golgi membranes, and it leads to substantial inhibition of Golgimediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterolbinding protein (OSBP), and ceramide-transfer protein (CERT), which interact with VAPs via their FFAT motif. The effect of VAPs on PI4P levels is mediated by the phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required for Golgi targeting of OSBP and CERT and the subsequent production of diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities. INTRODUCTIONThe unique lipid compositions of the secretory and endocytic organelles are critical for maintaining their distinct structural and functional identities (van Meer, 2000). Their identities are maintained despite extensive interconnecting vesicular-trafficking pathways, and they require tight regulation of lipid sorting, metabolism, and transport (van Meer, 1993;Pomorski et al., 2001;van Meer and Sprong, 2004). Increasing lines of evidence suggest that lipid-transfer proteins (LTPs) play a major role in regulating the lipid composition of membranous organelles (Sprong et al., 2001;De Matteis et al., 2007). These proteins facilitate lipid transfer between a donor and acceptor membrane (Holthuis and Levine, 2005), and they usually contain dual-targeting determinants for different membrane compartments. LTPs have been proposed to efficiently transfer lipids at membrane contact sites (MCSs) (Holthuis and Levine, 2005;Levine and Loewen, 2006).MCSs or zones of close apposition between the ER membranes and other cellular membranes, including the plasma membrane (PM), the membranes of the vacuoles, mitochondria, peroxisomes, lipid droplets, late endosomes, lysosomes, and the Golgi apparatus, have been identified in all eukaryotes by morphological and biochemical studies (Shore and Tata, 1977;Levine, 2004;Levine and Loewen, 2006). More recently, electron tomography studies have identified close contacts (10 -20 nm) between the ER and the outer mitochondrial membrane (Perkins et al., 1997) and between a specialized trans-ER and the three trans-most cisternae of the Golgi complex (Ladinsky et al., 1999;Marsh et al., 2001Marsh et al., , 2004. This ...

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Lipid distribution and transport across cellular membranes

Cited by 129 publications

References 75 publications

Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers

Tuning lipid mixtures to induce or suppress domain formation across leaflets of unsupported asymmetric bilayers

The IL1α-S100A13 Heterotetrameric Complex Structure

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

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