Key Points
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Cargo that has been internalized by endocytosis is often recycled to the plasma membrane after being sorted in endosomes.
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Many proteins and lipids of the plasma membrane are internalized using clathrin-independent mechanisms.
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Studies of cargo that is internalized independently of clathrin have revealed new pathways and mechanisms of recycling.
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Precise temporal and spatial regulation of recycling pathways is crucial for diverse cellular processes, including cytokinesis, cell adhesion, morphogenesis, cell fusion, learning and memory.
Abstract
Endocytic recycling is coordinated with endocytic uptake to control the composition of the plasma membrane. Although much of our understanding of endocytic recycling has come from studies on the transferrin receptor, a protein internalized through clathrin-dependent endocytosis, increased interest in clathrin-independent endocytosis has led to the discovery of new endocytic recycling systems. Recent insights into the regulatory mechanisms that control endocytic recycling have focused on recycling through tubular carriers and the return to the cell surface of cargoes that enter cells through clathrin-independent mechanisms. Recent work emphasizes the importance of regulated recycling in processes as diverse as cytokinesis, cell adhesion, morphogenesis, cell fusion, learning and memory.
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References
Steinman, R. M., Mellman, I. S., Muller, W. A. & Cohn, Z. A. Endocytosis and the recycling of plasma membrane. J. Cell Biol. 96, 1–27 (1983).
Conner, S. D. & Schmid, S. L. Regulated portals of entry into the cell. Nature 422, 37–44 (2003).
Doherty, G. J. & McMahon, H. T. Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902 (2009).
Mayor, S. & Pagano, R. E. Pathways of clathrin-independent endocytosis. Nature Rev. Mol. Cell Biol. 8, 603–612 (2007).
Sandvig, K., Torgersen, M. L., Raa, H. A. & van Deurs, B. Clathrin-independent endocytosis: from nonexisting to an extreme degree of complexity. Histochem. Cell Biol. 129, 267–276 (2008).
Swanson, J. A. Shaping cups into phagosomes and macropinosomes. Nature Rev. Mol. Cell Biol. 9, 639–649 (2008).
Donaldson, J. G., Porat-Shliom, N. & Cohen, L. A. Clathrin-independent endocytosis: a unique platform for cell signaling and PM remodeling. Cell Signal. 21, 1–6 (2009).
Maxfield, F. R. & McGraw, T. E. Endocytic recycling. Nature Rev. Mol. Cell Biol. 5, 121–132 (2004).
Gruenberg, J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).
Slagsvold, T., Pattni, K., Malerod, L. & Stenmark, H. Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol. 16, 317–326 (2006).
Woodman, P. G. & Futter, C. E. Multivesicular bodies: co-ordinated progression to maturity. Curr. Opin. Cell Biol. 20, 408–414 (2008).
Johannes, L. & Popoff, V. Tracing the retrograde route in protein trafficking. Cell 135, 1175–1187 (2008).
Kumari, S. & Mayor, S. ARF1 is directly involved in dynamin-independent endocytosis. Nature Cell Biol. 10, 30–41 (2008).
Radhakrishna, H. & Donaldson, J. G. ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway. J. Cell Biol. 139, 49–61 (1997).
Brown, F. D., Rozelle, A. L., Yin, H. L., Balla, T. & Donaldson, J. G. Phosphatidylinositol 4, 5-bisphosphate and Arf6-regulated membrane traffic. J. Cell Biol. 154, 1007–1017 (2001).
Powelka, A. M. et al. Stimulation-dependent recycling of integrin β1 regulated by ARF6 and Rab11. Traffic 5, 20–36 (2004).
Naslavsky, N., Weigert, R. & Donaldson, J. G. Characterization of a nonclathrin endocytic pathway: membrane cargo and lipid requirements. Mol. Biol. Cell 15, 3542–3552 (2004).
Eyster, C. A. et al. Discovery of new cargo proteins that enter cells through clathrin-independent endocytosis. Traffic 10, 590–599 (2009). This study identified endogenous plasma membrane proteins that enter human cells by CIE, thereby providing new cargo proteins that can be examined in different cell types.
Barral, D. C. et al. CD1a and MHC class I follow a similar endocytic recycling pathway. Traffic 9, 1446–1457 (2008).
Scarselli, M. & Donaldson, J. G. Constitutive internalization of G protein-coupled receptors and G proteins via clathrin-independent endocytosis. J. Biol. Chem. 284, 3577–3585 (2009).
Zimmermann, P. et al. Syndecan recycling is controlled by syntenin-PIP2 interaction and Arf6. Dev. Cell 9, 377–388 (2005). First report of specific intracellular sorting of the cargo protein syndecan in CIE by phosphoinositides, syntenin and ARF6.
Walseng, E., Bakke, O. & Roche, P. A. MHC class II-peptide complexes internalize using a clathrin- and dynamin-independent endocytosis pathway. J. Biol. Chem. 283, 14717–14727 (2008).
Gong, Q. et al. Identification and characterization of a new class of trafficking motifs for controlling clathrin-independent internalization and recycling. J. Biol. Chem. 282, 13087–13097 (2007).
Chen, C. C. et al. RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine. Mol. Biol. Cell 17, 1286–1297 (2006).
Shi, A. et al. A novel requirement for C. elegans Alix/ALX-1 in RME-1-mediated membrane transport. Curr. Biol. 17, 1913–1924 (2007). New role for ALX-1 (homologous to Bro1 in yeast), previously implicated in MVB formation, in RME-1-regulated endocytic recycling.
D' Souza-Schorey, C. & Chavrier, P. ARF proteins: roles in membrane traffic and beyond. Nature Rev. Mol. Cell Biol. 7, 347–358 (2006).
Grant, B. D. & Caplan, S. Mechanisms of EHD/RME-1 protein function in endocytic transport. Traffic 9, 2043–2052 (2008).
Daumke, O. et al. Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling. Nature 449, 923–927 (2007).
Balklava, Z., Pant, S., Fares, H. & Grant, B. D. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nature Cell Biol. 9, 1066–1073 (2007). Genome-wide analysis of genes involved in endocytosis and recycling in C. elegans , finding a role for polarity proteins in CDE and for cargo recycling in CIE.
Fares, H. & Greenwald, I. Genetic analysis of endocytosis in Caenorhabditis elegans: coelomocyte uptake defective mutants. Genetics 159, 133–145 (2001).
Grant, B. & Hirsh, D. Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol. Biol. Cell 10, 4311–4326 (1999).
Shaw, J. D., Cummings, K. B., Huyer, G., Michaelis, S. & Wendland, B. Yeast as a model system for studying endocytosis. Exp. Cell Res. 271, 1–9 (2001).
Choudhury, A., Sharma, D. K., Marks, D. L. & Pagano, R. E. Elevated endosomal cholesterol levels in Niemann–Pick cells inhibit rab4 and perturb membrane recycling. Mol. Biol. Cell 15, 4500–4511 (2004).
van der Sluijs, P. et al. The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway. Cell 70, 729–740 (1992).
Deneka, M. et al. Rabaptin-5α/rabaptin-4 serves as a linker between rab4 and γ1-adaptin in membrane recycling from endosomes. EMBO J. 22, 2645–2657 (2003).
Yudowski, G. A., Puthenveedu, M. A., Henry, A. G. & von Zastrow, M. Cargo-mediated regulation of a rapid rab4-dependent recycling pathway. Mol. Biol. Cell 20, 2774–2784 (2009).
Kouranti, I., Sachse, M., Arouche, N., Goud, B. & Echard, A. Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr. Biol. 16, 1719–1725 (2006).
Sato, M. et al. Regulation of endocytic recycling by C. elegans Rab35 and its regulator RME-4, a coated-pit protein. EMBO J. 27, 1183–1196 (2008).
Allaire, P. D. et al. Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-coated vesicles functioning in synaptic vesicle endocytosis. J. Neurosci. 26, 13202–13212 (2006).
Patino-Lopez, G. et al. Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation. J. Biol. Chem. 283, 18323–18330 (2008).
Sonnichsen, B., De Renzis, S., Nielsen, E., Rietdorf, J. & Zerial, M. Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5 and Rab11. J. Cell Biol. 149, 901–913 (2000).
Sharma, M., Naslavsky, N. & Caplan, S. A role for EHD4 in the regulation of early endosomal transport. Traffic 9, 995–1018 (2008).
Naslavsky, N., Rahajeng, J., Sharma, M., Jovic, M. & Caplan, S. Interactions between EHD proteins and Rab11-FIP2: a role for EHD3 in early endosomal transport. Mol. Biol. Cell 17, 163–177 (2006). Reports on the interaction of EHD1 and EHD3 with the same RAB11 effector, RAB11FIP2, leading to spatially distinct functions of these scaffolding proteins.
Schonteich, E. et al. The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling. J. Cell Sci. 121, 3824–3833 (2008).
Horgan, C. P. et al. Rab11-FIP3 is critical for the structural integrity of the endosomal recycling compartment. Traffic 8, 414–430 (2007).
Inoue, H., Ha, V. L., Prekeris, R. & Randazzo, P. A. Arf GTPase-activating protein ASAP1 interacts with Rab11 effector FIP3 and regulates pericentrosomal localization of transferrin receptor-positive recycling endosome. Mol. Biol. Cell 19, 4224–4237 (2008).
Magadan, J. G., Barbieri, M. A., Mesa, R., Stahl, P. D. & Mayorga, L. S. Rab22a regulates the sorting of transferrin to recycling endosomes. Mol. Cell. Biol. 26, 2595–2614 (2006).
Babbey, C. M. et al. Rab10 regulates membrane transport through early endosomes of polarized Madin–Darby canine kidney cells. Mol. Biol. Cell 17, 3156–3175 (2006).
Pelham, H. R. Insights from yeast endosomes. Curr. Opin. Cell Biol. 14, 454–462 (2002).
Traer, C. J. et al. SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment. Nature Cell Biol. 9, 1370–1380 (2007). Reports that SNX4 promotes dynein minus end-directed movement of early endosomes towards the ERC.
Lau, A. W. & Chou, M. M. The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway. J. Cell Sci. 121, 4008–4017 (2008).
Naslavsky, N., Weigert, R. & Donaldson, J. G. Convergence of non-clathrin- and clathrin-derived endosomes involves Arf6 inactivation and changes in phosphoinositides. Mol. Biol. Cell 14, 417–431 (2003).
Weigert, R., Yeung, A. C., Li, J. & Donaldson, J. G. Rab22a regulates the recycling of membrane proteins internalized independently of clathrin. Mol. Biol. Cell 15, 3758–3770 (2004). Shows that cargo recycling back to the plasma membrane in CIE requires RAB11, RAB22 and actin, distinguishing it from TFR recycling processes.
Balasubramanian, N., Scott, D. W., Castle, J. D., Casanova, J. E. & Schwartz, M. A. Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts. Nature Cell Biol. 9, 1381–1391 (2007).
Jovanovic, O. A., Brown, F. D. & Donaldson, J. G. An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling. Mol. Biol. Cell 17, 327–335 (2006).
Robertson, S. E. et al. Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. Mol. Biol. Cell 17, 645–657 (2006). Provides evidence that ERK signalling stimulates cargo recycling back to the plasma membrane in CIE.
Karacsonyi, C., Miguel, A. S. & Puertollano, R. Mucolipin-2 localizes to the Arf6-associated pathway and regulates recycling of GPI-APs. Traffic 8, 1404–1414 (2007).
Li, J. et al. An ACAP1-containing clathrin coat complex for endocytic recycling. J. Cell Biol. 178, 453–464 (2007).
Montagnac, G. et al. ARF6 interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis. Curr. Biol. 19, 184–195 (2009). Evidence that ARF6 can control the direction of endosomal movement by binding to the JIP scaffolding proteins, which bind to either dynein or kinesin.
Prigent, M. et al. ARF6 controls post-endocytic recycling through its downstream exocyst complex effector. J. Cell Biol. 163, 1111–1121 (2003).
Hattula, K. et al. Characterization of the Rab8-specific membrane traffic route linked to protrusion formation. J. Cell Sci. 119, 4866–4877 (2006).
Folsch, H., Pypaert, M., Maday, S., Pelletier, L. & Mellman, I. The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains. J. Cell Biol. 163, 351–362 (2003).
Thompson, A. et al. Recycling endosomes of polarized epithelial cells actively sort apical and basolateral cargos into separate subdomains. Mol. Biol. Cell 18, 2687–2697 (2007). Provides evidence for the segregation of recycling cargoes into separate subdomains in the recycling endosome.
Caplan, S. et al. A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane. EMBO J. 21, 2557–2567 (2002).
Grant, B. et al. Evidence that RME-1, a conserved C. elegans EH-domain protein, functions in endocytic recycling. Nature Cell Biol. 3, 573–579 (2001).
Lin, S. X., Grant, B., Hirsh, D. & Maxfield, F. R. Rme-1 regulates the distribution and function of the endocytic recycling compartment in mammalian cells. Nature Cell Biol. 3, 567–572 (2001).
Jovic, M., Kieken, F., Naslavsky, N., Sorgen, P. L. & Caplan, S. Eps15 homology domain 1-associated tubules contain phosphatidylinositol-4-phosphate and phosphatidylinositol-(4, 5)-bisphosphate and are required for efficient recycling. Mol. Biol. Cell 20, 2731–2743 (2009).
Braun, A. et al. EHD proteins associate with syndapin I and II and such interactions play a crucial role in endosomal recycling. Mol. Biol. Cell 16, 3642–3658 (2005).
Welsch, S. et al. Ultrastructural analysis of ESCRT proteins suggests a role for endosome-associated tubular-vesicular membranes in ESCRT function. Traffic 7, 1551–1566 (2006).
Yan, Q. et al. mVps24p functions in EGF receptor sorting/trafficking from the early endosome. Exp. Cell Res. 304, 265–273 (2005).
Boucrot, E. & Kirchhausen, T. Endosomal recycling controls plasma membrane area during mitosis. Proc. Natl Acad. Sci. USA 104, 7939–7944 (2007). Shows that reduced recycling occurs during mitosis, which contributes to a reduced plasma membrane area and the rounding up of dividing cells.
Van Damme, D., Inze, D. & Russinova, E. Vesicle trafficking during somatic cytokinesis. Plant Physiol. 147, 1544–1552 (2008).
Jantsch-Plunger, V. & Glotzer, M. Depletion of syntaxins in the early Caenorhabditis elegans embryo reveals a role for membrane fusion events in cytokinesis. Curr. Biol. 9, 738–745 (1999).
Xu, H. et al. Syntaxin 5 is required for cytokinesis and spermatid differentiation in Drosophila. Dev. Biol. 251, 294–306 (2002).
Low, S. H. et al. Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. Dev. Cell 4, 753–759 (2003).
Glotzer, M. The molecular requirements for cytokinesis. Science 307, 1735–1739 (2005).
Montagnac, G., Echard, A. & Chavrier, P. Endocytic traffic in animal cell cytokinesis. Curr. Opin. Cell Biol. 20, 454–461 (2008).
Skop, A. R., Bergmann, D., Mohler, W. A. & White, J. G. Completion of cytokinesis in C. elegans requires a brefeldin A-sensitive membrane accumulation at the cleavage furrow apex. Curr. Biol. 11, 735–746 (2001).
Riggs, B. et al. Actin cytoskeleton remodeling during early Drosophila furrow formation requires recycling endosomal components Nuclear-fallout and Rab11. J. Cell Biol. 163, 143–154 (2003).
Fielding, A. B. et al. Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis. EMBO J. 24, 3389–3399 (2005).
Schweitzer, J. K. & D' Souza-Schorey, C. Localization and activation of the ARF6 GTPase during cleavage furrow ingression and cytokinesis. J. Biol. Chem. 277, 27210–27216 (2002).
Dyer, N. et al. Spermatocyte cytokinesis requires rapid membrane addition mediated by ARF6 on central spindle recycling endosomes. Development 134, 4437–4447 (2007).
Hickson, G. R. et al. Arfophilins are dual Arf/Rab11 binding proteins that regulate recycling endosome distribution and are related to Drosophila nuclear fallout. Mol. Biol. Cell 14, 2908–2920 (2003).
Grosshans, J. et al. RhoGEF2 and the formin Dia control the formation of the furrow canal by directed actin assembly during Drosophila cellularisation. Development 132, 1009–1020 (2005).
Padash Barmchi, M., Rogers, S. & Hacker, U. DRhoGEF2 regulates actin organization and contractility in the Drosophila blastoderm embryo. J. Cell Biol. 168, 575–585 (2005).
Cao, J., Albertson, R., Riggs, B., Field, C. M. & Sullivan, W. Nuf, a Rab11 effector, maintains cytokinetic furrow integrity by promoting local actin polymerization. J. Cell Biol. 182, 301–313 (2008).
Simon, G. C. et al. Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis. EMBO J. 27, 1791–1803 (2008).
Arden, S. D., Puri, C., Au, J. S., Kendrick-Jones, J. & Buss, F. Myosin VI is required for targeted membrane transport during cytokinesis. Mol. Biol. Cell 18, 4750–4761 (2007).
Roux, A., Uyhazi, K., Frost, A. & De Camilli, P. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Nature 441, 528–531 (2006).
Lin, S. X., Gundersen, G. G. & Maxfield, F. R. Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesin. Mol. Biol. Cell 13, 96–109 (2002).
Paterson, A. D., Parton, R. G., Ferguson, C., Stow, J. L. & Yap, A. S. Characterization of E-cadherin endocytosis in isolated MCF-7 and chinese hamster ovary cells: the initial fate of unbound E-cadherin. J. Biol. Chem. 278, 21050–21057 (2003).
Palacios, F., Price, L., Schweitzer, J., Collard, J. G. & D'Souza-Schorey, C. An essential role for ARF6-regulated membrane traffic in adherens junction turnover and epithelial cell migration. EMBO J. 20, 4973–4986 (2001).
Lock, J. G. & Stow, J. L. Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin. Mol. Biol. Cell 16, 1744–1755 (2005).
Bryant, D. M. et al. EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin. J. Cell Sci. 120, 1818–1828 (2007).
Langevin, J. et al. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-cadherin trafficking from recycling endosomes to the plasma membrane. Dev. Cell 9, 365–376 (2005).
Ribeiro, C., Ebner, A. & Affolter, M. In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis. Dev. Cell 2, 677–683 (2002).
Shaye, D. D., Casanova, J. & Llimargas, M. Modulation of intracellular trafficking regulates cell intercalation in the Drosophila trachea. Nature Cell Biol. 10, 964–970 (2008). Connects morphological events in development with the temporal and spatial regulation of the underlying recycling endosome machinery.
Harris, K. P. & Tepass, U. Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis. J. Cell Biol. 183, 1129–1143 (2008).
Duncan, M. C. & Peifer, M. Regulating polarity by directing traffic: Cdc42 prevents adherens junctions from Crumblin' aPart. J. Cell Biol. 183, 971–974 (2008).
Georgiou, M., Marinari, E., Burden, J. & Baum, B. Cdc42, Par6, and aPKC regulate Arp2/3-mediated endocytosis to control local adherens junction stability. Curr. Biol. 18, 1631–1638 (2008).
Leibfried, A., Fricke, R., Morgan, M. J., Bogdan, S. & Bellaiche, Y. Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis. Curr. Biol. 18, 1639–1648 (2008).
Erickson, M. R., Galletta, B. J. & Abmayr, S. M. Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J. Cell Biol. 138, 589–603 (1997).
Pajcini, K. V., Pomerantz, J. H., Alkan, O., Doyonnas, R. & Blau, H. M. Myoblasts and macrophages share molecular components that contribute to cell–cell fusion. J. Cell Biol. 180, 1005–1019 (2008).
Grassart, A., Dujeancourt, A., Lazarow, P. B., Dautry-Varsat, A. & Sauvonnet, N. Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2. EMBO Rep. 9, 356–362 (2008).
Chen, E. H., Pryce, B. A., Tzeng, J. A., Gonzalez, G. A. & Olson, E. N. Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Cell 114, 751–762 (2003).
Palamidessi, A. et al. Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134, 135–147 (2008).
Doherty, K. R. et al. The endocytic recycling protein EHD2 interacts with myoferlin to regulate myoblast fusion. J. Biol. Chem. 283, 20252–20260 (2008).
Derkach, V. A., Oh, M. C., Guire, E. S. & Soderling, T. R. Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nature Rev. Neurosci. 8, 101–113 (2007).
Park, M., Penick, E. C., Edwards, J. G., Kauer, J. A. & Ehlers, M. D. Recycling endosomes supply AMPA receptors for LTP. Science 305, 1972–1975 (2004).
Wang, Z. et al. Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity. Cell 135, 535–548 (2008). Elegant study that shows how NMDAR-stimulated calcium levels allow myosin Vb to associate with RAB11FIP2-positive endosomes bearing AMPARs, facilitating their delivery to dendritic spines.
Chung, H. J. et al. G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation. Proc. Natl Acad. Sci. USA 106, 635–640 (2009).
Brown, T. C., Correia, S. S., Petrok, C. N. & Esteban, J. A. Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation. J. Neurosci. 27, 13311–13315 (2007).
Gerges, N. Z., Backos, D. S. & Esteban, J. A. Local control of AMPA receptor trafficking at the postsynaptic terminal by a small GTPase of the Rab family. J. Biol. Chem. 279, 43870–43878 (2004).
Glodowski, D. R., Chen, C. C., Schaefer, H., Grant, B. D. & Rongo, C. RAB-10 regulates glutamate receptor recycling in a cholesterol-dependent endocytosis pathway. Mol. Biol. Cell 18, 4387–4396 (2007).
Ang, A. L. et al. Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells. J. Cell Biol. 167, 531–543 (2004).
Murray, R. Z., Kay, J. G., Sangermani, D. G. & Stow, J. L. A role for the phagosome in cytokine secretion. Science 310, 1492–1495 (2005).
Hao, M. M. et al. Vesicular and non-vesicular sterol transport in living cells. The endocytic recycling compartment is a major sterol storage organelle. J. Biol. Chem. 277, 609–617 (2002).
Padron, D., Tall, R. D. & Roth, M. G. Phospholipase D2 is required for efficient endocytic recycling of transferrin receptors. Mol. Biol. Cell 17, 598–606 (2006).
Jordens, I., Marsman, M., Kuijl, C. & Neefjes, J. Rab proteins, connecting transport and vesicle fusion. Traffic 6, 1070–1077 (2005).
Pfeffer, S. R. Structural clues to Rab GTPase functional diversity. J. Biol. Chem. 280, 15485–15488 (2005).
Jones, M. C., Caswell, P. T. & Norman, J. C. Endocytic recycling pathways: emerging regulators of cell migration. Curr. Opin. Cell Biol. 18, 549–557 (2006).
Cohen, L. A. et al. Active Arf6 recruits ARNO/cytohesin GEFs to the PM by binding their PH domains. Mol. Biol. Cell 18, 2244–2253 (2007).
Chies, R. et al. Alterations in the Arf6-regulated plasma membrane endosomal recycling pathway in cells overexpressing the tetraspan protein Gas3/PMP22. J. Cell Sci. 116, 987–999 (2003).
Lavezzari, G. & Roche, K. W. Constitutive endocytosis of the metabotropic glutamate receptor mGluR7 is clathrin-independent. Neuropharmacology 52, 100–107 (2007).
Acknowledgements
We apologize to colleagues whose work we could not cite owing to length restrictions. We thank S. Caplan and members of the Grant and Donaldson laboratories for comments. B.D.G. is supported by National Institutes of Health (NIH) grant R01 GM067237. J.G.D. is supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, NIH.
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Glossary
- Macropinocytosis
-
An actin-dependent process by which cells engulf large volumes of fluids.
- Phagocytosis
-
An actin-dependent process by which cells engulf external particulate material by extension and fusion of pseudopods.
- Multivesicular body
-
An endocytic intermediate organelle in the lysosomal degradative pathway that contains small vesicles and is surrounded by a limiting membrane.
- Lipid raft
-
A microdomain in cellular membranes that is implicated in certain types of endocytosis and signalling and that is enriched in cholesterol and sphingolipids.
- ESCRT
-
(Endosomal sorting complex required for transport). A multiprotein machinery that promotes inward vesiculation at the limiting membrane of the sorting endosome and selects cargo proteins for delivery to the intralumenal vesicles of MVBs.
- DENN domain
-
(Differentially expressed in neoplastic versus normal cells domain). A domain present in many proteins that are involved in vesicle trafficking.
- Clathrin-coated pit
-
The initial site of invagination of a clathrin-coated vesicle.
- GTPase-activating protein
-
A protein that catalyses GTP hydrolysis on GTP-bound proteins.
- Immunological synapse
-
A junction that forms at the contact region between a T cell and its target cells. T cell activation occurs here.
- Sorting nexin
-
A member of a family of proteins that are implicated in membrane trafficking and that contain a Phox domain, which binds to phosphoinositides.
- Syndecan
-
A member of a family of integral membrane heparin sulphate proteoglycans that interact with the extracellular matrix and with growth factors.
- PDZ domain
-
A protein interaction domain that is often found in scaffolding proteins and that is named after the founding members of this protein family (PSD95, Discs large and ZO1).
- Guanine nucleotide exchange factor
-
A protein that facilitates the exchange of GDP (guanine diphosphate) for GTP (guanine triphosphate) in the nucleotide-binding pocket of a GTP-binding protein.
- Exocyst
-
A complex of proteins, forming a membrane tether, that is implicated in exocytosis and is localized to the plasma membrane.
- Intercalation
-
The interdigitation of cells or molecules in a reversible reaction.
- Adherens junction
-
A cell–cell adhesion complex that contains cadherins and catenins that are attached to cytoplasmic actin filaments.
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Grant, B., Donaldson, J. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10, 597–608 (2009). https://doi.org/10.1038/nrm2755
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DOI: https://doi.org/10.1038/nrm2755
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Tailoring tumor-recognizable hyaluronic acid–lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells
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Emerging applications of extracellular vesicles in tumor therapy
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