Membrane curvature is no longer seen as a passive consequence of cellular activity but an active means to create membrane domains and to organize centres for membrane trafficking. Curvature can be dynamically modulated by changes in lipid composition, the oligomerization of curvature scaffolding proteins and the reversible insertion of protein regions that act like wedges in membranes. There is an interplay between curvature-generating and curvature-sensing proteins during vesicle budding. This is seen during vesicle budding and in the formation of microenvironments. On a larger scale, membrane curvature is a prime player in growth, division and movement.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rothman, J. E. & Orci, L. Budding vesicles in living cells. Scient. Am. 274, 70–75 (1996).
Sciaky, N. et al. Golgi tubule traffic and the effects of brefeldin A visualized in living cells. J. Cell Biol. 139, 1137–1155 (1997).
Heuser, J. Three-dimensional visualization of coated vesicle formation in fibroblasts. J. Cell Biol. 84, 560–583 (1980).
Bright, N. A., Gratian, M. J. & Luzio, J. P. Endocytic delivery to lysosomes mediated by concurrent fusion and kissing events in living cells. Curr. Biol. 15, 360–365 (2005).
Singer, S. J. & Nicolson, G. L. The fluid mosaic model of the structure of cell membranes. Science 175, 720–731 (1972).
Kusumi, A. et al. Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu. Rev. Biophys. Biomol. Struct. 34, 351–378 (2005).
Stowell, M. H., Marks, B., Wigge, P. & McMahon, H. T. Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring. Nature Cell Biol. 1, 27–32 (1999).
Baumgart, T., Hess, S. T. & Webb, W. W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824 (2003).
Bacia, K., Schwille, P. & Kurzchalia, T. Sterol structure determines the separation of phases and the curvature of the liquid-ordered phase in model membranes. Proc. Natl Acad. Sci. USA 102, 3272–3277 (2005).
Kooijman, E. E. et al. Spontaneous curvature of phosphatidic acid and lysophosphatidic acid. Biochemistry 44, 2097–2102 (2005).
Brown, W. J., Chambers, K. & Doody, A. Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic 4, 214–221 (2003).
Shemesh, T., Luini, A., Malhotra, V., Burger, K. N. & Kozlov, M. M. Prefission constriction of Golgi tubular carriers driven by local lipid metabolism: a theoretical model. Biophys. J. 85, 3813–3827 (2003).
Farge, E., Ojcius, D. M., Subtil, A. & Dautry-Varsat, A. Enhancement of endocytosis due to aminophospholipid transport across the plasma membrane of living cells. Am. J. Physiol. 276, C725–C733 (1999).
Hua, Z. & Graham, T. R. Requirement for neo1p in retrograde transport from the Golgi complex to the endoplasmic reticulum. Mol. Biol. Cell 14, 4971–4983 (2003).
Hammond, K., Reboiras, M. D., Lyle, I. G. & Jones, M. N. Characterisation of phosphatidylcholine/phosphatidylinositol sonicated vesicles. Effects of phospholipid composition on vesicle size. Biochim. Biophys. Acta 774, 19–25 (1984).
Ford, M. G. et al. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science 291, 1051–1055 (2001).
Ford, M. G. et al. Curvature of clathrin-coated pits driven by epsin. Nature 419, 361–366 (2002).
Kinuta, M. et al. Phosphatidylinositol 4,5-bisphosphate stimulates vesicle formation from liposomes by brain cytosol. Proc. Natl Acad. Sci. USA 99, 2842–2847 (2002).
Wenk, M. R. & De Camilli, P. Protein–lipid interactions and phosphoinositide metabolism in membrane traffic: insights from vesicle recycling in nerve terminals. Proc. Natl Acad. Sci. USA 101, 8262–8269 (2004).
Honing, S. et al. Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Mol. Cell 18, 519–531 (2005).
Fernandez-Borja, M. et al. Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity. Curr. Biol. 9, 55–58 (1999).
Gruenberg, J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).
Odorizzi, G., Babst, M. & Emr, S. D. Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95, 847–858 (1998).
Roux, A. et al. Role of curvature and phase transition in lipid sorting and fission of membrane tubules. EMBO J. 24, 1537–1545 (2005).
Cremona, O. et al. Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 99, 179–188 (1999).
Fertuck, H. C. & Salpeter, M. M. Localization of acetylcholine receptor by 125I-labeled alpha-bungarotoxin binding at mouse motor endplates. Proc. Natl Acad. Sci. USA 71, 1376–1378 (1974).
Unwin, N. Refined structure of the nicotinic acetylcholine receptor at 4Å resolution. J. Mol. Biol. 346, 967–989 (2005).
Mackinnon, R. Structural biology. Voltage sensor meets lipid membrane. Science 306, 1304–1305 (2004).
Boudin, H. et al. Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron 28, 485–497 (2000).
Eckler, S. A., Kuehn, R. & Gautam, M. Deletion of N-terminal rapsyn domains disrupts clustering and has dominant negative effects on clustering of full-length rapsyn. Neuroscience 131, 661–670 (2005).
Kirchhausen, T., Boll, W., van Oijen, A. & Ehrlich, M. Single-molecule live-cell imaging of clathrin-based endocytosis. Biochem. Soc. Symp. 72, 71–76 (2005).
Petrou, S. et al. Direct effects of fatty acids and other charged lipids on ion channel activity in smooth muscle cells. Prostaglandins Leukot. Essent. Fatty Acids 52, 173–178 (1995).
Casado, M. & Ascher, P. Opposite modulation of NMDA receptors by lysophospholipids and arachidonic acid: common features with mechanosensitivity. J. Physiol. 513, 317–330 (1998).
Fuster, D., Moe, O. W. & Hilgemann, D. W. Lipid- and mechanosensitivities of sodium/hydrogen exchangers analyzed by electrical methods. Proc. Natl Acad. Sci. USA 101, 10482–10487 (2004).
Ledesma, M. D. & Dotti, C. G. Membrane and cytoskeleton dynamics during axonal elongation and stabilization. Int. Rev. Cytol. 227, 183–219 (2003).
Sheetz, M. P. Cell control by membrane-cytoskeleton adhesion. Nature Rev. Mol. Cell Biol. 2, 392–396 (2001).
Raucher, D. & Sheetz, M. P. Cell spreading and lamellipodial extension rate is regulated by membrane tension. J. Cell Biol. 148, 127–136 (2000).
Dai, J., Ting-Beall, H. P. & Sheetz, M. P. The secretion-coupled endocytosis correlates with membrane tension changes in RBL 2H3 cells. J. Gen. Physiol. 110, 1–10 (1997).
Heidelberger, R., Zhou, Z. Y. & Matthews, G. Multiple components of membrane retrieval in synaptic terminals revealed by changes in hydrostatic pressure. J. Neurophysiol. 88, 2509–2517 (2002).
Raucher, D. & Sheetz, M. P. Membrane expansion increases endocytosis rate during mitosis. J. Cell Biol. 144, 497–506 (1999).
Bettache, N. et al. Mechanical constraint imposed on plasma membrane through transverse phospholipid imbalance induces reversible actin polymerization via phosphoinositide 3-kinase activation. J. Cell Sci. 116, 2277–2284 (2003).
Merrifield, C. J., Perrais, D. & Zenisek, D. Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells. Cell 121, 593–606 (2005).
Yarar, D., Waterman-Storer, C. M. & Schmid, S. L. A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis. Mol. Biol. Cell 16, 964–975 (2005).
Shupliakov, O. et al. Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton. Proc. Natl Acad. Sci. USA 99, 14476–14481 (2002).
Engqvist-Goldstein, A. E. et al. RNAi-mediated Hip1R silencing results in stable association between the endocytic machinery and the actin assembly machinery. Mol. Biol. Cell 15, 1666–1679 (2004).
Qualmann, B. & Kelly, R. B. Syndapin isoforms participate in receptor-mediated endocytosis and actin organization. J. Cell Biol. 148, 1047–1062 (2000).
Rodriguez-Boulan, E., Kreitzer, G. & Musch, A. Organization of vesicular trafficking in epithelia. Nature Rev. Mol. Cell Biol. 6, 233–247 (2005).
Vale, R. D. & Hotani, H. Formation of membrane networks in vitro by kinesin-driven microtubule movement. J. Cell Biol. 107, 2233–2241 (1988).
Dabora, S. L. & Sheetz, M. P. The microtubule-dependent formation of a tubulovesicular network with characteristics of the ER from cultured cell extracts. Cell 54, 27–35 (1988).
Buss, F., Luzio, J. P. & Kendrick-Jones, J. Myosin VI, an actin motor for membrane traffic and cell migration. Traffic 3, 851–858 (2002).
Bretscher, M. S. Getting membrane flow and the cytoskeleton to cooperate in moving cells. Cell 87, 601–606 (1996).
Allan, V. & Vale, R. Movement of membrane tubules along microtubules in vitro: evidence for specialised sites of motor attachment. J. Cell Sci. 107, 1885–1897 (1994).
Merrifield, C. J. Seeing is believing: imaging actin dynamics at single sites of endocytosis. Trends Cell Biol. 14, 352–358 (2004).
Zakharenko, S. & Popov, S. Dynamics of axonal microtubules regulate the topology of new membrane insertion into the growing neurites. J. Cell Biol. 143, 1077–1086 (1998).
Peter, B. J. et al. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499 (2004).
Hinshaw, J. E. & Schmid, S. L. Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature 374, 190–192 (1995).
Marks, B. et al. GTPase activity of dynamin and resulting conformation change are essential for endocytosis. Nature 410, 231–235 (2001).
Praefcke, G. J. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nature Rev. Mol. Cell Biol. 5, 133–147 (2004).
Sweitzer, S. M. & Hinshaw, J. E. Dynamin undergoes a GTP-dependent conformational change causing vesiculation. Cell 93, 1021–1029 (1998).
von Schwedler, U. K. et al. The protein network of HIV budding. Cell 114, 701–713 (2003).
Antonny, B., Gounon, P., Schekman, R. & Orci, L. Self-assembly of minimal COPII cages. EMBO Rep. 4, 419–424 (2003).
Nossal, R. Energetics of clathrin basket assembly. Traffic 2, 138–147 (2001).
Razani, B. & Lisanti, M. P. Caveolins and caveolae: molecular and functional relationships. Exp. Cell Res. 271, 36–44 (2001).
Zimmerberg, J. & McLaughlin, S. Membrane curvature: how BAR domains bend bilayers. Curr. Biol. 14, R250–R252 (2004).
Takei, K., Slepnev, V. I., Haucke, V. & De Camilli, P. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nature Cell Biol. 1, 33–39 (1999).
Farsad, K. et al. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J. Cell Biol. 155, 193–200 (2001).
Razzaq, A. et al. Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila. Genes Dev. 15, 2967–2979 (2001).
Richnau, N., Fransson, A., Farsad, K. & Aspenstrom, P. RICH-1 has a BIN/Amphiphysin/Rvsp domain responsible for binding to membrane lipids and tubulation of liposomes. Biochem. Biophys. Res. Commun. 320, 1034–1042 (2004).
Wigge, P. et al. Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis. Mol. Biol. Cell 8, 2003–2015 (1997).
Carlton, J. et al. Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high-curvature membranes and 3-phosphoinositides. Curr. Biol. 14, 1791–1800 (2004).
Orcl, L., Palmer, D. J., Amherdt, M. & Rothman, J. E. Coated vesicle assembly in the Golgi requires only coatomer and ARF proteins from the cytosol. Nature 364, 732–734 (1993).
Seaman, M. N., Sowerby, P. J. & Robinson, M. S. Cytosolic and membrane-associated proteins involved in the recruitment of AP-1 adaptors onto the trans-Golgi network. J. Biol. Chem. 271, 25446–25451 (1996).
Puertollano, R., Randazzo, P. A., Presley, J. F., Hartnell, L. M. & Bonifacino, J. S. The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Cell 105, 93–102 (2001).
Bi, X., Corpina, R. A. & Goldberg, J. Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat. Nature 419, 271–277 (2002).
Mashl, R. J. & Bruinsma, R. F. Spontaneous-curvature theory of clathrin-coated membranes. Biophys. J. 74, 2862–2875 (1998).
Kozlov, M. M. Fission of biological membranes: interplay between dynamin and lipids. Traffic 2, 51–65 (2001).
Bigay, J., Gounon, P., Robineau, S. & Antonny, B. Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature. Nature 426, 563–566 (2003).
Bigay, J., Casella, J. F., Drin, G., Mesmin, B. & Antonny, B. ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif. EMBO J. 24, 2244–2253 (2005).
Antonny, B., Beraud-Dufour, S., Chardin, P. & Chabre, M. N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange. Biochemistry 36, 4675–4684 (1997).
Kobayashi, T. et al. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193–197 (1998).
Matsuo, H. et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 303, 531–534 (2004).
Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT.-I. Cell 106, 145–155 (2001).
Odorizzi, G., Katzmann, D. J., Babst, M., Audhya, A. & Emr, S. D. Bro1 is an endosome-associated protein that functions in the MVB pathway in Saccharomyces cerevisiae. J. Cell Sci. 116, 1893–1903 (2003).
Kim, J. et al. Structural basis for endosomal targeting by the bro1 domain. Dev. Cell 8, 937–947 (2005).
Ward, D. M. et al. The role of LIP5 and CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells. J. Biol. Chem. 280, 10548–10555 (2005).
Praefcke, G. J. et al. Evolving nature of the AP2 alpha-appendage hub during clathrin-coated vesicle endocytosis. EMBO J. 23, 4371–4383 (2004).
Perry, M. M. & Gilbert, A. B. Yolk transport in the ovarian follicle of the hen (Gallus domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase. J. Cell Sci. 39, 257–272 (1979).
Gallop, J. L. & McMahon, H. T. BAR domains and membrane curvature: bringing your curves to the BAR. Biochem. Soc. Symp. 72, 223–231 (2005).
Jao, C. C., Der-Sarkissian, A., Chen, J. & Langen, R. Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling. Proc. Natl Acad. Sci. USA 101, 8331–8336 (2004).
Lee, S. et al. De novo-designed peptide transforms Golgi-specific lipids into Golgi-like nanotubules. J. Biol. Chem. 276, 41224–41228 (2001).
Stahelin, R. V. et al. Contrasting membrane interaction mechanisms of AP180 N-terminal homology (ANTH) and epsin N-terminal homology (ENTH) domains. J. Biol. Chem. 278, 28993–28999 (2003).
B. Peter provided inspiration for this review, and although he has moved on to better things, his thoughts and contribution were invaluable. He is largely responsible for Fig. 3. We also thank P. Evans and all members of the laboratory for their continuous curvature discussion. J.G. was the recipient of an MRC Predoctoral Fellowship and Karn Fund Postdoctoral Fellowship.
The authors declare no competing financial interests.
Author Information Reprints and permissions information is available at npg.nature.com/reprintsandpermissions.
About this article
Cite this article
McMahon, H., Gallop, J. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005). https://doi.org/10.1038/nature04396
Soft Matter (2020)
Soft Matter (2020)
Genes to Cells (2020)
The lipid raft markers stomatin, prohibitin, flotillin, and HflK/C (SPFH)-domain proteins form an operon with NfeD proteins and function with apolar polyisoprenoid lipids
Critical Reviews in Microbiology (2020)
Frontiers in Microbiology (2020)