Key Points
-
Non-vesicular lipid transport plays a crucial part in intracellular lipid trafficking and can be mediated by spontaneous lipid transport or by lipid-transfer proteins (LTPs).
-
LTPs markedly facilitate (by several orders of magnitude) the transport of lipids between membranes in vitro.
-
Non-vesicular lipid transport is thought to be greatly enhanced at membrane contact sites; small cytosolic gaps between the endoplasmic reticulum membrane and virtually all other cellular organelles.
-
LTPs do not mediate a simple vectorial lipid transport from one membrane to another. Rather, they facilitate lipid transport between membranes according to their membrane environment.
-
LTPs use their lipid-transfer activity to regulate various cellular processes, including vesicular trafficking, signal transduction and lipid metabolism.
Abstract
The movement of lipids within and between intracellular membranes is mediated by different lipid transport mechanisms and is crucial for maintaining the identities of different cellular organelles. Non-vesicular lipid transport has a crucial role in intracellular lipid trafficking and distribution, but its underlying mechanisms remain unclear. Lipid-transfer proteins (LTPs), which regulate diverse lipid-mediated cellular processes and accelerate vectorial transport of lipid monomers between membranes in vitro, could potentially mediate non-vesicular intracellular lipid trafficking. Understanding the mechanisms by which lipids are transported and distributed between cellular membranes, and elucidating the role of LTPs in intracellular lipid transport and homeostasis, are currently subjects of intensive study.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Holthuis, J. C., van Meer, G. & Huitema, K. Lipid microdomains, lipid translocation and the organization of intracellular membrane transport (Review). Mol. Membr. Biol. 20, 231–241 (2003).
Sprong, H., van der Sluijs, P. & van Meer, G. How proteins move lipids and lipids move proteins. Nature Rev. Mol. Cell Biol. 2, 504–513 (2001).
Voelker, D. R. Organelle biogenesis and intracellular lipid transport in eukaryotes. Microbiol. Rev. 55, 543–560 (1991).
van Meer, G. Lipid traffic in animal cells. Annu. Rev. Cell Biol. 5, 247–275 (1989).
Pomorski, T., Hrafnsdottir, S., Devaux, P. F. & van Meer, G. Lipid distribution and transport across cellular membranes. Semin. Cell Dev. Biol. 12, 139–148 (2001).
Sleight, R. G. Intracellular lipid transport in eukaryotes. Annu. Rev. Physiol. 49, 193–208 (1987).
Voelker, D. R. Lipid transport pathways in mammalian cells. Experientia 46, 569–579 (1990).
Kaplan, M. R. & Simoni, R. D. Intracellular transport of phosphatidylcholine to the plasma membrane. J. Cell Biol. 101, 441–445 (1985).
Vance, J. E., Aasman, E. J. & Szarka, R. Brefeldin A does not inhibit the movement of phosphatidylethanolamine from its sites for synthesis to the cell surface. J. Biol. Chem. 266, 8241–8247 (1991).
Holthuis, J. C. & Levine, T. P. Lipid traffic: floppy drives and a superhighway. Nature Rev. Mol. Cell Biol. 6, 209–220 (2005).
Levine, T. Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions. Trends Cell Biol. 14, 483–490 (2004).
Kawano, M., Kumagai, K., Nishijima, M. & Hanada, K. Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J. Biol. Chem. 281, 30279–30288 (2006). This paper provides molecular insight into CERT-mediated ceramide transport at ER–Golgi MCSs.
Funato, K. & Riezman, H. Vesicular and nonvesicular transport of ceramide from ER to the Golgi apparatus in yeast. J. Cell Biol. 155, 949–959 (2001).
Hanada, K. Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide. Mol. Cell Biochem. 286, 23–31 (2006).
Lebiedzinska, M., Szabadkai, G., Jones, A. W., Duszynski, J. & Wieckowski, M. R. Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles. Int. J. Biochem. Cell Biol. 41, 1805–1816 (2009).
Jones, J. D. & Thompson, T. E. Spontaneous phosphatidylcholine transfer by collision between vesicles at high lipid concentration. Biochemistry 28, 129–134 (1989).
Mesmin, B. & Maxfield, F. R. Intracellular sterol dynamics. Biochim. Biophys. Acta 1791, 636–645 (2009).
Zilversmit, D. B. Lipid transfer proteins: overview and applications. Methods Enzymol. 98, 565–573 (1983).
Helmkamp, G. M. Jr. Phospholipid transfer proteins: mechanism of action. J. Bioenerg. Biomembr. 18, 71–91 (1986).
Wirtz, K. W. & Zilversmit, D. B. Exchange of phospholipids between liver mitochondria and microsomes in vitro. J. Biol. Chem. 243, 3596–3602 (1968).
D'Angelo, G., Vicinanza, M. & De Matteis, M. A. Lipid-transfer proteins in biosynthetic pathways. Curr. Opin. Cell Biol. 20, 360–370 (2008).
Fairn, G. D. & McMaster, C. R. Emerging roles of the oxysterol-binding protein family in metabolism, transport, and signaling. Cell. Mol. Life Sci. 65, 228–236 (2008).
De Matteis, M. A., Di Campli, A. & D'Angelo, G. Lipid-transfer proteins in membrane trafficking at the Golgi complex. Biochim. Biophys. Acta 1771, 761–768 (2007).
Cockcroft, S. Mammalian phosphatidylinositol transfer proteins: emerging roles in signal transduction and vesicular traffic. Chem. Phys. Lipids 98, 23–33 (1999).
Perkins, G. et al. Electron tomography of neuronal mitochondria: three-dimensional structure and organization of cristae and membrane contacts. J. Struct. Biol. 119, 260–272 (1997).
Lev, S. Lipid homoeostasis and Golgi secretory function. Biochem. Soc. Trans. 34, 363–366 (2006).
Nichols, J. W. & Pagano, R. E. Kinetics of soluble lipid monomer diffusion between vesicles. Biochemistry 20, 2783–2789 (1981).
McLean, L. R. & Phillips, M. C. Mechanism of cholesterol and phosphatidylcholine exchange or transfer between unilamellar vesicles. Biochemistry 20, 2893–2900 (1981).
McLean, L. R. & Phillips, M. C. Kinetics of phosphatidylcholine and lysophosphatidylcholine exchange between unilamellar vesicles. Biochemistry 23, 4624–4630 (1984).
Phillips, M. C., Johnson, W. J. & Rothblat, G. H. Mechanisms and consequences of cellular cholesterol exchange and transfer. Biochim. Biophys. Acta 906, 223–276 (1987).
Massey, J. B. et al. Measurement and prediction of the rates of spontaneous transfer of phospholipids between plasma lipoproteins. Biochim. Biophys. Acta 794, 274–280 (1984).
Bai, J. & Pagano, R. E. Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles. Biochemistry 36, 8840–8848 (1997).
McLean, L. R. & Phillips, M. C. Cholesterol transfer from small and large unilamellar vesicles. Biochim. Biophys. Acta 776, 21–26 (1984).
Radhakrishnan, A. & McConnell, H. M. Chemical activity of cholesterol in membranes. Biochemistry 39, 8119–8124 (2000).
Roseman, M. A. & Thompson, T. E. Mechanism of the spontaneous transfer of phospholipids between bilayers. Biochemistry 19, 439–444 (1980).
Martin, F. J. & MacDonald, R. C. Phospholipid exchange between bilayer membrane vesicles. Biochemistry 15, 321–327 (1976).
Steck, T. L., Kezdy, F. J. & Lange, Y. An activation-collision mechanism for cholesterol transfer between membranes. J. Biol. Chem. 263, 13023–13031 (1988).
Gadella, T. W. Jr & Wirtz, K. W. Phospholipid binding and transfer by the nonspecific lipid-transfer protein (sterol carrier protein 2). A kinetic model. Eur. J. Biochem. 220, 1019–1028 (1994).
Lalanne, F. & Ponsin, G. Mechanism of the phospholipid transfer protein-mediated transfer of phospholipids from model lipid vesicles to high density lipoproteins. Biochim. Biophys. Acta 1487, 82–91 (2000).
Gadella, T. W. Jr & Wirtz, K. W. The low-affinity lipid binding site of the non-specific lipid transfer protein. Implications for its mode of action. Biochim. Biophys. Acta 1070, 237–245 (1991).
Nichols, J. W. Kinetics of fluorescent-labeled phosphatidylcholine transfer between nonspecific lipid transfer protein and phospholipid vesicles. Biochemistry 27, 1889–1896 (1988).
Kumagai, K. et al. CERT mediates intermembrane transfer of various molecular species of ceramides. J. Biol. Chem. 280, 6488–6495 (2005).
Alpy, F. & Tomasetto, C. Give lipids a START: the StAR-related lipid transfer (START) domain in mammals. J. Cell Sci. 118, 2791–2801 (2005).
Yamaji, T., Kumagai, K., Tomishige, N. & Hanada, K. Two sphingolipid transfer proteins, CERT and FAPP2: their roles in sphingolipid metabolism. IUBMB Life 60, 511–518 (2008).
Wirtz, K. W., Schouten, A. & Gros, P. Phosphatidylinositol transfer proteins: from closed for transport to open for exchange. Adv. Enzyme Regul. 46, 301–311 (2006).
Im, Y. J., Raychaudhuri, S., Prinz, W. A. & Hurley, J. H. Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature 437, 154–158 (2005). The crystal structure of Osh4 was resolved in this study, and the mechanisms by which Osh4 mediates sterol transport and interacts with membranes were proposed.
Feng, L., Chan, W. W., Roderick, S. L. & Cohen, D. E. High-level expression and mutagenesis of recombinant human phosphatidylcholine transfer protein using a synthetic gene: evidence for a C-terminal membrane binding domain. Biochemistry 39, 15399–15409 (2000).
Arakane, F. et al. Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondrial import sequence: implications for the mechanism of StAR action. Proc. Natl Acad. Sci. USA 93, 13731–13736 (1996).
Wirtz, K. W. Phospholipid transfer proteins. Annu. Rev. Biochem. 60, 73–99 (1991).
Wirtz, K. W., Vriend, G. & Westerman, J. Kinetic analysis of the interaction of the phosphatidylcholine exchange protein with unilamellar vesicels and multilamellar liposomes. Eur. J. Biochem. 94, 215–221 (1979).
Rueckert, D. G. & Schmidt, K. Lipid transfer proteins. Chem. Phys. Lipids 56, 1–20 (1990).
Kasper, A. M. & Helmkamp, G. M. Jr. Intermembrane phospholipid fluxes catalyzed by bovine brain phospholipid exchange protein. Biochim. Biophys. Acta 664, 22–32 (1981).
Wirtz, K. W., Devaux, P. F. & Bienvenue, A. Phosphatidylcholine exchange protein catalyzes the net transfer of phosphatidylcholine to model membranes. Biochemistry 19, 3395–3399 (1980).
Zilversmit, D. B. Lipid transfer proteins. J. Lipid Res. 25, 1563–1569 (1984).
Li, H., Tremblay, J. M., Yarbrough, L. R. & Helmkamp, G. M. Jr. Both isoforms of mammalian phosphatidylinositol transfer protein are capable of binding and transporting sphingomyelin. Biochim. Biophys. Acta 1580, 67–76 (2002).
Mattjus, P. Glycolipid transfer proteins and membrane interaction. Biochim. Biophys. Acta 1788, 267–272 (2009).
Tilley, S. J. et al. Structure-function analysis of phosphatidylinositol transfer protein a bound to human phosphatidylinositol. Structure 12, 317–326 (2004).
Shadan, S. et al. Dynamics of lipid transfer by phosphatidylinositol transfer proteins in cells. Traffic 9, 1743–1756 (2008).
Kudo, N. et al. Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proc. Natl Acad. Sci. USA 105, 488–493 (2008).
Phillips, S. E., Ile, K. E., Boukhelifa, M., Huijbregts, R. P. & Bankaitis, V. A. Specific and nonspecific membrane-binding determinants cooperate in targeting phosphatidylinositol transfer protein b-isoform to the mammalian trans-Golgi network. Mol. Biol. Cell 17, 2498–2512 (2006).
Schulz, T. A. et al. Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues. J. Cell Biol. 187, 889–903 (2009).
Levine, T. P. & Munro, S. The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes. Curr. Biol. 8, 729–739 (1998).
Ngo, M. & Ridgway, N. D. Oxysterol binding protein-related protein 9 (ORP9) is a cholesterol transfer protein that regulates Golgi structure and function. Mol. Biol. Cell 20, 1388–1399 (2009).
Levine, T. & Loewen, C. Inter-organelle membrane contact sites: through a glass, darkly. Curr. Opin. Cell Biol. 18, 371–378 (2006).
Voelker, D. R. Bridging gaps in phospholipid transport. Trends Biochem. Sci. 30, 396–404 (2005).
Giorgi, C., De Stefani, D., Bononi, A., Rizzuto, R. & Pinton, P. Structural and functional link between the mitochondrial network and the endoplasmic reticulum. Int. J. Biochem. Cell Biol. 41, 1817–1827 (2009).
Kornmann, B. et al. An ER–mitochondria tethering complex revealed by a synthetic biology screen. Science 325, 477–481 (2009). This study used an elegant synthetic biology screen in yeast and identified an ER–mitochondrion tethering complex, the ERMES, which is essential for inter-organelle phospholipid transport.
de Brito, O. M. & Scorrano, L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456, 605–610 (2008).
Szabadkai, G. et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J. Cell Biol. 175, 901–911 (2006).
Kvam, E. & Goldfarb, D. S. Nvj1p is the outer-nuclear-membrane receptor for oxysterol-binding protein homolog Osh1p in Saccharomyces cerevisiae. J. Cell Sci. 117, 4959–4968 (2004).
Anderie, I., Schulz, I. & Schmid, A. Direct interaction between ER membrane-bound PTP1B and its plasma membrane-anchored targets. Cell Signal. 19, 582–592 (2007).
Wu, M. M., Buchanan, J., Luik, R. M. & Lewis, R. S. Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J. Cell Biol. 174, 803–813 (2006).
Yuan, J. P. et al. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114, 777–789 (2003).
Lehto, M. et al. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Exp. Cell Res. 310, 445–462 (2005).
Rocha, N. et al. Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150Glued and late endosome positioning. J. Cell Biol. 185, 1209–1225 (2009).
Stone, S. J. & Vance, J. E. Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes. J. Biol. Chem. 275, 34534–34540 (2000).
Daum, G. & Vance, J. E. Import of lipids into mitochondria. Prog. Lipid Res. 36, 103–130 (1997).
Hanada, K., Kumagai, K., Tomishige, N. & Kawano, M. CERT and intracellular trafficking of ceramide. Biochim. Biophys. Acta 1771, 644–653 (2007).
Loewen, C. J., Roy, A. & Levine, T. P. A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J. 22, 2025–2035 (2003). This study identified a new motif, FFAT, in various LTPs that mediates the interaction with the ER through binding of the integral ER membrane proteins of the VAP family.
Lev, S., Ben Halevy, D., Peretti, D. & Dahan, N. The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol. 18, 282–290 (2008).
Hanada, K. et al. Molecular machinery for non-vesicular trafficking of ceramide. Nature 426, 803–809 (2003). CERT, which was cloned in this study, was shown to have a major role in intracellular ceramide transport and, therefore, sphingomyelin production.
Perry, R. J. & Ridgway, N. D. Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein. Mol. Biol. Cell 17, 2604–2616 (2006).
Amarilio, R., Ramachandran, S., Sabanay, H. & Lev, S. Differential regulation of endoplasmic reticulum structure through VAP–Nir protein interaction. J. Biol. Chem. 280, 5934–5944 (2005).
Peretti, D., Dahan, N., Shimoni, E., Hischberg, K. & Lev, S. Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol. Biol. Cell 19, 3871–3884 (2008).
Maxfield, F. R. & Mondal, M. Sterol and lipid trafficking in mammalian cells. Biochem. Soc. Trans. 34, 335–339 (2006). An insightful review on sterol transport in cells that provides interesting quantitative data and calculations.
Hynynen, R. et al. Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. Biochem. J. 390, 273–283 (2005).
Ikonen, E. & Jansen, M. Cellular sterol trafficking and metabolism: spotlight on structure. Curr. Opin. Cell Biol. 20, 371–377 (2008).
Raychaudhuri, S., Im, Y. J., Hurley, J. H. & Prinz, W. A. Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides. J. Cell Biol. 173, 107–119 (2006).
Pagano, R. E. What is the fate of diacylglycerol produced at the Golgi apparatus? Trends Biochem. Sci. 13, 202–205 (1988).
Baron, C. L. & Malhotra, V. Role of diacylglycerol in PKD recruitment to the TGN and protein transport to the plasma membrane. Science 295, 325–328 (2002).
Hausser, A. et al. Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIβ at the Golgi complex. Nature Cell Biol. 7, 880–886 (2005).
Wang, Y. J. et al. Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell 114, 299–310 (2003).
Fugmann, T. et al. Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J. Cell Biol. 178, 15–22 (2007).
Harris, W. A. & Stark, W. S. Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. J. Gen. Physiol. 69, 261–291 (1977).
Hotta, Y., Benzer, S. Abnormal electroretinogram in visual mutants in Drosophila. Nature 222, 354–356 (1969).
Hardie, R. C. et al. Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors. Neuron 30, 149–159 (2001).
Milligan, S. C., Alb, J. G. Jr, Elagina, R. B., Bankaitis, V. A. & Hyde, D. R. The phosphatidylinositol transfer protein domain of Drosophila retinal degeneration B protein is essential for photoreceptor cell survival and recovery from light stimulation. J. Cell Biol. 139, 351–363 (1997).
Vihtelic, T. S., Goebl, M., Milligan, S., O'Tousa, J. E. & Hyde, D. R. Localization of Drosophila retinal degeneration B, a membrane-associated phosphatidylinositol transfer protein. J. Cell Biol. 122, 1013–1022 (1993).
Bankaitis, V. A., Aitken, J. R., Cleves, A. E. & Dowhan, W. An essential role for a phospholipid transfer protein in yeast Golgi function. Nature 347, 561–562 (1990).
Bankaitis, V. A., Malehorn, D. E., Emr, S. D. & Greene, R. The Saccharomyces cerevisiae SEC14 gene encodes a cytosolic factor that is required for transport of secretory proteins from the yeast Golgi complex. J. Cell Biol. 108, 1271–1281 (1989).
Cleves, A. E. et al. Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cell 64, 789–800 (1991). A functional link between Sec14 and the CDP-choline pathway was shown here by a genetic approach that led to the isolation of 'bypass-Sec14' mutants.
Kearns, B. G. et al. Essential role for diacylglycerol in protein transport from the yeast Golgi complex. Nature 387, 101–105 (1997).
Skinner, H. B. et al. The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity. Proc. Natl Acad. Sci. USA 92, 112–116 (1995).
McGee, T. P., Skinner, H. B., Whitters, E. A., Henry, S. A. & Bankaitis, V. A. A phosphatidylinositol transfer protein controls the phosphatidylcholine content of yeast Golgi membranes. J. Cell Biol. 124, 273–287 (1994).
Litvak, V., Dahan, N., Ramachandran, S., Sabanay, H. & Lev, S. Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function. Nature Cell Biol. 7, 225–234 (2005).
Schaaf, G. et al. Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the Sec14 superfamily. Mol. Cell 29, 191–206 (2008). This study provides mechanistic insights into PtdIns–PtdCho exchange by Sec14 and its dual role in sensing PtdCho and presenting PtdIns to control phosphoinositide homeostasis.
Wang, P. Y., Weng, J. & Anderson, R. G. OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307, 1472–1476 (2005).
Fairn, G. D., Curwin, A. J., Stefan, C. J. & McMaster, C. R. The oxysterol binding protein Kes1p regulates Golgi apparatus phosphatidylinositol-4- phosphate function. Proc. Natl Acad. Sci. USA 104, 15352–15357 (2007).
Li, X. et al. Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. J. Cell Biol. 157, 63–77 (2002).
Ferrell, J. E. Jr, Lee, K. J. & Huestis, W. H. Lipid transfer between phosphatidylcholine vesicles and human erythrocytes: exponential decrease in rate with increasing acyl chain length. Biochemistry 24, 2857–2864 (1985).
Schouten, A. et al. Structure of apo-phosphatidylinositol transfer protein a provides insight into membrane association. EMBO J. 21, 2117–2121 (2002).
Yoder, M. D. et al. Structure of a multifunctional protein. Mammalian phosphatidylinositol transfer protein complexed with phosphatidylcholine. J. Biol. Chem. 276, 9246–9252 (2001).
D'Angelo, G. et al. Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature 449, 62–67 (2007).
Halter, D. et al. Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis. J. Cell Biol. 179, 101–115 (2007).
Acknowledgements
Sima Lev is the incumbent of the Joyce and Ben B. Eisenberg Chair of Molecular Biology and Cancer Research. This work was supported by the Israel Science Foundation, Grant number 548/08. The author thanks R. Sertchook from the Weizmann Institute of Science for assistance in collecting the three-dimensional images, A. Menon and O. Laufman for productive discussion, and especially W. Prinz for the critical reading of this manuscript and his intellectual contribution.
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The author declares no competing financial interests.
Supplementary information
Supplementary Information S1 (Table)
Apparent half-time (h) for [3H]POPC (1-palmitoyl-2-oleoyl PC) transfer at 37 °C as a function of donor concentration for the indicated acceptor concentrations. (PDF 148 kb)
Supplementary Information S2 (Box)
Measurement of Lipid Transfer Activity in vitro (PDF 234 kb)
Supplementary Information S3 (Figure)
Structure of selected sterols and PtdCho species (PDF 97 kb)
Related links
Glossary
- Vesicular transport
-
An active process in which materials move into or out of the cell enclosed in vesicles. This process is mediated by a sequence of events involving the budding of the vesicles from a donor membrane and their subsequent fusion with an acceptor membrane.
- Peroxisome
-
An organelle present in most eukaryotic cells that is involved in the oxidation of fatty acids and the production and destruction of hydrogen peroxide.
- Lipid desorption
-
The release of a lipid molecule from a lipid bilayer to the surrounding aqueous phase. This process involves both the disruption of lipid–lipid interactions in the bilayer and the formation of a cavity in the aqueous phase that accommodates the diffusing lipid molecule.
- Vectorial lipid transport
-
A directional transport of lipids that is driven by a concentration gradient.
- Lipid droplet
-
An organelle that stores neutral lipids and has a crucial role in lipid metabolism.
- Flippase
-
A membrane protein that catalyses the transport of lipids across the membrane bilayer in an ATP-dependent manner. Flippases commonly transport lipids towards the cytoplasm, whereas floppases transport lipids from the cytofacial surface to the opposite side of the membrane.
- Membrane curvature
-
The bending of the membrane, which can be influenced by the relative distribution of cone-like and inverted cone-like lipids (for example, diacylglcerol and phosphatidic acid, and lysophospholipids, respectively) between the inner or outer leaflets of the bilayer.
- Vesicle fission
-
The pinching-off of a vesicle from a membrane bilayer.
- Vesicle fusion
-
The merging of a vesicle with a membrane bilayer.
- Condensed complex
-
A complex formed between cholesterol and saturated phospholipids with long fatty acid chains or with sphingomyelin.
- First-order process
-
A reaction with a rate that is proportional to the concentration of only one reactant. Other reactants can be present but have no influence on the reaction rate.
- Second-order process
-
A reaction with a rate that is proportional to the square concentration of a single reactant or to the concentration of two reactants.
- Thermal motion
-
The random motion of lipid molecules in the bilayer that is due to temperature.
- Hydration force
-
The repulsive force acting between apposing lipid bilayers in aqueous solution.
- Liposome
-
An artificial microscopic vesicle consisting of an aqueous core surrounded by a lipid bilayer.
- Membrane fluidity
-
The viscosity of the lipid bilayer, which is determined by the length and saturation of the fatty-acid side chains of phospholipids and the content of cholesterol and sphingolipids..
- Phosphoinositide
-
The phosphorylated form of PtdIns. The inositol ring of PtdIns can be phosphorylated in three different positions (3, 4 and 5), yielding seven distinct phosphoinositides. Phosphoinositides play a key part in signal transduction and membrane trafficking.
- PH domain
-
A protein domain of ∼100 amino acids that is present in numerous proteins and in many cases binds phosphoinositides with high affinity and specificity.
- FFAT motif
-
A short sequence motif, containing the EFFDAxE consensus sequence, that has been identified in 17 eukaryotic proteins, most of which are involved in lipid transfer, sensing or binding.
- PtdIns-transfer domain
-
A protein domain that is present in PITPs and mediates the exchange of PtdIns for PtdCho, and vice versa. PITPs have a ∼16-fold higher binding affinity for PtdIns than PtdCho.
- Steroidogenesis
-
The biosynthesis of steroid hormones.
- AP1 complex
-
A heterotetrameric complex with a role in protein sorting at the trans-Golgi network and endosomes. AP1 mediates the recruitment of clathrin to membranes and the recognition of sorting signals in the cytosolic tails of transmembrane cargo proteins.
Rights and permissions
About this article
Cite this article
Lev, S. Non-vesicular lipid transport by lipid-transfer proteins and beyond. Nat Rev Mol Cell Biol 11, 739–750 (2010). https://doi.org/10.1038/nrm2971
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrm2971
This article is cited by
-
HRG-9 homologues regulate haem trafficking from haem-enriched compartments
Nature (2022)
-
A brief history of how microscopic studies led to the elucidation of the 3D architecture and macromolecular organization of higher plant thylakoids
Photosynthesis Research (2020)
-
Enhanced monoterpene emission in transgenic orange mint (Mentha × piperita f. citrata) overexpressing a tobacco lipid transfer protein (NtLTP1)
Planta (2020)
-
Distribution, dynamics and functional roles of phosphatidylserine within the cell
Cell Communication and Signaling (2019)
-
Endogenous alpha-synuclein monomers, oligomers and resulting pathology: let’s talk about the lipids in the room
npj Parkinson's Disease (2019)