cell membrane coated pits

Summary

Summary: Specialized regions of the cell membrane composed of pits coated with a bristle covering made of the protein CLATHRIN. These pits are the entry route for macromolecules bound by cell surface receptors. The pits are then internalized into the cytoplasm to form the COATED VESICLES.

Top Publications

  1. Pearse B, Smith C, Owen D. Clathrin coat construction in endocytosis. Curr Opin Struct Biol. 2000;10:220-8 pubmed
  2. Santini F, Gaidarov I, Keen J. G protein-coupled receptor/arrestin3 modulation of the endocytic machinery. J Cell Biol. 2002;156:665-76 pubmed
  3. Tebar F, Bohlander S, Sorkin A. Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol Biol Cell. 1999;10:2687-702 pubmed
    ..Altogether, the data suggest that CALM is an important component of coated pit internalization machinery, possibly involved in the regulation of clathrin recruitment to the membrane and/or the formation of the coated pit. ..
  4. Chin D, Straubinger R, Acton S, Nathke I, Brodsky F. 100-kDa polypeptides in peripheral clathrin-coated vesicles are required for receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1989;86:9289-93 pubmed
    ..This demonstrates an in situ function of these polypeptides and the protein complexes in which they are found. ..
  5. Kirchhausen T. Clathrin. Annu Rev Biochem. 2000;69:699-727 pubmed
    ..This review summarizes and illustrates the recent structural results and outlines what is known about coated-vesicle assembly in the context of this information. ..
  6. Greener T, Zhao X, Nojima H, Eisenberg E, Greene L. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. J Biol Chem. 2000;275:1365-70 pubmed
    ..We propose that GAK is a required cofactor for the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. ..
  7. Lamaze C, Dujeancourt A, Baba T, Lo C, Benmerah A, Dautry Varsat A. Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway. Mol Cell. 2001;7:661-71 pubmed
    ..These results define novel properties of receptor-mediated endocytosis and establish that the IL2 receptor is efficiently internalized through this clathrin-independent pathway. ..
  8. Stang E, Blystad F, Kazazic M, Bertelsen V, Brodahl T, Raiborg C, et al. Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits. Mol Biol Cell. 2004;15:3591-604 pubmed
  9. Mettlen M, Stoeber M, Loerke D, Antonescu C, Danuser G, Schmid S. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009;20:3251-60 pubmed publisher

More Information

Publications72

  1. Merrifield C, Feldman M, Wan L, Almers W. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nat Cell Biol. 2002;4:691-8 pubmed
    ..Therefore, dynamin may provide the trigger and actin may provide the force for movement into the cytosol. ..
  2. Warnock D, Schmid S. Dynamin GTPase, a force-generating molecular switch. Bioessays. 1996;18:885-93 pubmed
    ..In this case, dynamin would be the first GTPase identified that acts as a structural protein with mechano-chemical function...
  3. Gaidarov I, Keen J. Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits. J Cell Biol. 1999;146:755-64 pubmed
    ..1999. EMBO (Eur. Mol. Biol. Organ.) J. 18:871-881), suggest that phosphoinositides play a critical and general role in adaptor incorporation into plasma membrane clathrin-coated pits...
  4. Kazazic M, Bertelsen V, Pedersen K, Vuong T, Grandal M, Rødland M, et al. Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits. Traffic. 2009;10:235-45 pubmed publisher
    ..Additionally, upon knockdown of epsin 1, translocation of the EGFR to central parts of clathrin-coated pits was inhibited. This supports the contention that epsin 1 promotes endocytosis of the ubiquitinated EGFR...
  5. Morris S, Cooper J. Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2. Traffic. 2001;2:111-23 pubmed
    ..These findings suggest that in addition to previously reported signal-transduction functions, Dab2 could also act as an adaptor protein that may regulate protein trafficking...
  6. Loerke D, Mettlen M, Yarar D, Jaqaman K, Jaqaman H, Danuser G, et al. Cargo and dynamin regulate clathrin-coated pit maturation. PLoS Biol. 2009;7:e57 pubmed publisher
    ..From these data, we infer the existence of an endocytic restriction or checkpoint, responsive to cargo and regulated by dynamin...
  7. Merrifield C, Qualmann B, Kessels M, Almers W. Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts. Eur J Cell Biol. 2004;83:13-8 pubmed
    ..We suggest that N-WASP and the Arp2/3 complex trigger actin polymerization during a late step in clathrin-mediated endocytosis, and propel clathrin-coated pits or vesicles from the plasma membrane into the cytoplasm...
  8. Benmerah A, Bayrou M, Cerf Bensussan N, Dautry Varsat A. Inhibition of clathrin-coated pit assembly by an Eps15 mutant. J Cell Sci. 1999;112 ( Pt 9):1303-11 pubmed
    ..This hypothesis is supported by the fact that a GFP fusion protein encoding the ear domain of (alpha)-adaptin, the AP-2 binding site for Eps15, was efficiently targeted to plasma membrane coated pits...
  9. Santini F, Marks M, Keen J. Endocytic clathrin-coated pit formation is independent of receptor internalization signal levels. Mol Biol Cell. 1998;9:1177-94 pubmed
    ..Rather, the findings support a model in which coated pit formation proceeds through recruitment and activation of AP2, likely through a limited number of regulated docking sites that act independently of endocytic signals...
  10. Merrifield C, Perrais D, Zenisek D. Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells. Cell. 2005;121:593-606 pubmed publisher
    ..We propose that CCP invagination, actin polymerization, and CCV formation are highly coordinated for efficient endocytosis...
  11. Brodsky F, Chen C, Knuehl C, Towler M, Wakeham D. Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol. 2001;17:517-68 pubmed
    ..Tissue-specific functions of CCVs require even more-specialized regulation and defects in these pathways can now be correlated with human diseases...
  12. Cheetham M, Anderton B, Jackson A. Inhibition of hsc70-catalysed clathrin uncoating by HSJ1 proteins. Biochem J. 1996;319 ( Pt 1):103-8 pubmed
    ..Although we find no evidence for auxilin in our coated vesicle preparation, our results predict that an auxilin-like protein will be a general factor in clathrin uncoating...
  13. Olusanya O, Andrews P, Swedlow J, Smythe E. Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo. Curr Biol. 2001;11:896-900 pubmed
    ..Here, we show that phosphorylation of a single threonine residue (Thr156) of the mu2 subunit of the AP2 complex is essential for efficient endocytosis of transferrin both in an in vitro coated-pit budding assay and in living cells...
  14. Itoh T, Koshiba S, Kigawa T, Kikuchi A, Yokoyama S, Takenawa T. Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. Science. 2001;291:1047-51 pubmed
    ..Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential for endocytosis mediated by clathrin-coated pits...
  15. Ford M, Mills I, Peter B, Vallis Y, Praefcke G, Evans P, et al. Curvature of clathrin-coated pits driven by epsin. Nature. 2002;419:361-6 pubmed
    ..We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations...
  16. Robinson M. Cloning and expression of gamma-adaptin, a component of clathrin-coated vesicles associated with the Golgi apparatus. J Cell Biol. 1990;111:2319-26 pubmed
  17. Sunyach C, Jen A, Deng J, Fitzgerald K, Frobert Y, Grassi J, et al. The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein. EMBO J. 2003;22:3591-601 pubmed
    ..The effect of this changing membrane environment upon the susceptibility of prion protein to pathogenic conversion is discussed...
  18. Voglmaier S, Keen J, Murphy J, Ferris C, Prestwich G, Snyder S, et al. Inositol hexakisphosphate receptor identified as the clathrin assembly protein AP-2. Biochem Biophys Res Commun. 1992;187:158-63 pubmed
    ..The IP6 receptor protein analyzed by SDS-PAGE contains a series of subunits which are the same as those of AP-2. Antibodies to AP-2 react with the IP6 receptor protein in immunoblot analysis...
  19. McNiven M, Cao H, Pitts K, Yoon Y. The dynamin family of mechanoenzymes: pinching in new places. Trends Biochem Sci. 2000;25:115-20 pubmed
    ..The potential contributions by the dynamin family to these diverse but related functions are discussed...
  20. Pauloin A, Thurieau C. The 50 kDa protein subunit of assembly polypeptide (AP) AP-2 adaptor from clathrin-coated vesicles is phosphorylated on threonine-156 by AP-1 and a soluble AP50 kinase which co-purifies with the assembly polypeptides. Biochem J. 1993;296 ( Pt 2):409-15 pubmed
    ..This AP50 kinase activity corresponded to a 280 kDa protein complex according to gel-filtration data...
  21. Motley A, Bright N, Seaman M, Robinson M. Clathrin-mediated endocytosis in AP-2-depleted cells. J Cell Biol. 2003;162:909-18 pubmed
    ..Uptake of the EGF and LDL receptors may be facilitated by alternative adaptors...
  22. Marsh M, McMahon H. The structural era of endocytosis. Science. 1999;285:215-20 pubmed
    ..Together, these data provide an initial three-dimensional framework for understanding the clathrin endocytic machinery...
  23. Mangasarian A, Foti M, Aiken C, Chin D, Carpentier J, Trono D. The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane. Immunity. 1997;6:67-77 pubmed
    ..Taken together, these data suggest that Nef down-regulates CD4 and probably MHC I by physically connecting these receptors with sorting pathways in the Golgi and at the plasma membrane...
  24. Benesch S, Polo S, Lai F, Anderson K, Stradal T, Wehland J, et al. N-WASP deficiency impairs EGF internalization and actin assembly at clathrin-coated pits. J Cell Sci. 2005;118:3103-15 pubmed
  25. Keyel P, Mishra S, Roth R, Heuser J, Watkins S, Traub L. A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Mol Biol Cell. 2006;17:4300-17 pubmed
    ..However, Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss. ..
  26. Rappoport J, Kemal S, Benmerah A, Simon S. Dynamics of clathrin and adaptor proteins during endocytosis. Am J Physiol Cell Physiol. 2006;291:C1072-81 pubmed
    ..These data also support a role for static clathrin, providing a nucleation site for endocytosis...
  27. Jiang X, Sorkin A. Epidermal growth factor receptor internalization through clathrin-coated pits requires Cbl RING finger and proline-rich domains but not receptor polyubiquitylation. Traffic. 2003;4:529-43 pubmed
    ..We propose that the RING domain of Cbl facilitates endocytosis either by epidermal growth factor receptor monoubiquitylation or by ubiquitylation of proteins associated with the receptor...
  28. Conner S, Schmid S. Differential requirements for AP-2 in clathrin-mediated endocytosis. J Cell Biol. 2003;162:773-9 pubmed
    ..Surprisingly, clathrin distribution and EGF uptake were unaffected by AAK1 overexpression. Thus, AP-2 may not be stoichiometrically required for coat assembly, and may have a more cargo-selective function in CME than previously thought...
  29. Ferguson S, Ferguson S, Raimondi A, Paradise S, Shen H, Mesaki K, et al. Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell. 2009;17:811-22 pubmed publisher
    ..Our data also demonstrate that the relationship between dynamin and actin is intimately connected to dynamin's endocytic role and that dynamin terminates a powerful actin- and BAR protein-dependent tubulating activity...
  30. Haucke V, De Camilli P. AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs. Science. 1999;285:1268-71 pubmed
    ..This suggests a mechanism by which nucleation of clathrin-coated pits is stimulated by the loading of cargo proteins...
  31. Bennett E, Chen C, Engqvist Goldstein A, Drubin D, Brodsky F. Clathrin hub expression dissociates the actin-binding protein Hip1R from coated pits and disrupts their alignment with the actin cytoskeleton. Traffic. 2001;2:851-8 pubmed
    ..These findings indicate that proper function of clathrin is required for coated pit alignment with the actin cytoskeleton and suggest that the clathrin-Hip1R interaction is involved in the cytoskeletal organization of coated pits...
  32. Chang M, Mallet W, Mostov K, Brodsky F. Adaptor self-aggregation, adaptor-receptor recognition and binding of alpha-adaptin subunits to the plasma membrane contribute to recruitment of adaptor (AP2) components of clathrin-coated pits. EMBO J. 1993;12:2169-80 pubmed
  33. Cremona O, Di Paolo G, Wenk M, Luthi A, Kim W, Takei K, et al. Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell. 1999;99:179-88 pubmed
    ..These results provide genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling...
  34. Santini F, Penn R, Gagnon A, Benovic J, Keen J. Selective recruitment of arrestin-3 to clathrin coated pits upon stimulation of G protein-coupled receptors. J Cell Sci. 2000;113 ( Pt 13):2463-70 pubmed
    ..Thus, this work demonstrates coupling of G protein-coupled receptors to a specific non-visual arrestin in an in vivo setting...
  35. Matsui W, Kirchhausen T. Stabilization of clathrin coats by the core of the clathrin-associated protein complex AP-2. Biochemistry. 1990;29:10791-8 pubmed
    ..These results are consistent with the proposal that the AP core contains the binding site(s) for clathrin, while the alpha- and beta-chain appendages interact with membrane components of coated pits and coated vesicles...
  36. Laporte S, Oakley R, Holt J, Barak L, Caron M. The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits. J Biol Chem. 2000;275:23120-6 pubmed
    ..These results reveal that the binding of a receptor-beta-arrestin complex to AP-2, not to clathrin, is necessary for the initial targeting of beta(2)-adrenergic receptor to clathrin-coated pits...
  37. Gallusser A, Kirchhausen T. The beta 1 and beta 2 subunits of the AP complexes are the clathrin coat assembly components. EMBO J. 1993;12:5237-44 pubmed
    ..It is proposed that the principal function of the beta subunits is to initiate coat formation, while the remaining subunits of the AP complexes have other roles in coated pit and coated vesicle function...
  38. Kosaka T, Ikeda K. Reversible blockage of membrane retrieval and endocytosis in the garland cell of the temperature-sensitive mutant of Drosophila melanogaster, shibirets1. J Cell Biol. 1983;97:499-507 pubmed
    ..The observations suggest that in the garland cell of shi the conversion of coated pits to coated vesicles, that is, membrane pinch-off, is blocked at high temperature...
  39. Sorkin A. Cargo recognition during clathrin-mediated endocytosis: a team effort. Curr Opin Cell Biol. 2004;16:392-9 pubmed
    ..These alternative mechanisms appear to be particularly important during clathrin-mediated endocytosis of signaling receptors...
  40. Legendre Guillemin V, Metzler M, Lemaire J, Philie J, Gan L, Hayden M, et al. Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain. J Biol Chem. 2005;280:6101-8 pubmed
    ..Interestingly, HIP1 binds to a highly conserved region of CLC previously demonstrated to regulate clathrin assembly. These results suggest a role for HIP1/CLC interactions in the regulation of clathrin assembly...
  41. Puthenveedu M, von Zastrow M. Cargo regulates clathrin-coated pit dynamics. Cell. 2006;127:113-24 pubmed
  42. Deinhardt K, Berninghausen O, Willison H, Hopkins C, Schiavo G. Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin1. J Cell Biol. 2006;174:459-71 pubmed
  43. Ford M, Pearse B, Higgins M, Vallis Y, Owen D, Gibson A, et al. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science. 2001;291:1051-5 pubmed
    ..This was shown by using purified components and a budding assay on preformed lipid monolayers. In the presence of AP180, clathrin lattices formed on the monolayer. When AP2 was also present, coated pits were formed...
  44. Huang B, Wang W, Bates M, Zhuang X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science. 2008;319:810-3 pubmed publisher
    ..This development allowed us to resolve the 3D morphology of nanoscopic cellular structures...
  45. Tosoni D, Puri C, Confalonieri S, Salcini A, De Camilli P, Tacchetti C, et al. TTP specifically regulates the internalization of the transferrin receptor. Cell. 2005;123:875-88 pubmed
    ..Thus, TTP might represent one of the long sought for molecules that allow cargo-specific control of clathrin endocytosis...
  46. Akisaka T, Yoshida H, Suzuki R, Takama K. Adhesion structures and their cytoskeleton-membrane interactions at podosomes of osteoclasts in culture. Cell Tissue Res. 2008;331:625-41 pubmed
    ..Thus, the clathrin plaques on the ventral membrane of osteoclasts might be involved in both cell adhesion and the formation of receptor-ligand complexes, i.e., endocytosis...
  47. Boucrot E, Saffarian S, Massol R, Kirchhausen T, Ehrlich M. Role of lipids and actin in the formation of clathrin-coated pits. Exp Cell Res. 2006;312:4036-48 pubmed
    ..Thus, remodeling of the actin cytoskeleton is not essential for clathrin-coated vesicle assembly but may indirectly affect the nucleation of clathrin-coated pits...
  48. Vieira A, Lamaze C, Schmid S. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science. 1996;274:2086-9 pubmed
    ..Thus, endocytic trafficking of activated EGFR plays a critical role not only in attenuating EGFR signaling but also in establishing and controlling specific signaling pathways...
  49. Coda L, Salcini A, Confalonieri S, Pelicci G, Sorkina T, Sorkin A, et al. Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits-mediated internalization. J Biol Chem. 1998;273:3003-12 pubmed
    ..We propose that eps15 and eps15R are multifunctional binding proteins that serve pleiotropic functions within the cell...
  50. Soulet F, Yarar D, Leonard M, Schmid S. SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell. 2005;16:2058-67 pubmed
    ..Thus, our results establish that SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity...
  51. Nichols B. GM1-containing lipid rafts are depleted within clathrin-coated pits. Curr Biol. 2003;13:686-90 pubmed
    ..The data provide evidence for a model in which lipid rafts are distributed uniformly across most of the PM of nonpolarized cells but are prevented from entering clathrin-coated pits...
  52. Tebar F, Sorkina T, Sorkin A, Ericsson M, Kirchhausen T. Eps15 is a component of clathrin-coated pits and vesicles and is located at the rim of coated pits. J Biol Chem. 1996;271:28727-30 pubmed
    ..These findings suggest several possible regulatory roles of Eps15 during the formation of coated pits...
  53. Haucke V. Phosphoinositide regulation of clathrin-mediated endocytosis. Biochem Soc Trans. 2005;33:1285-9 pubmed
    ..In this mini-review, I will discuss the pathways of PI(4,5)P2 formation and its interactions with endocytic trafficking adaptors...
  54. Lee D, Wu X, Eisenberg E, Greene L. Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J Cell Sci. 2006;119:3502-12 pubmed
    ..Therefore, budding as well as synchronous recruitment of GAK might be required for irreversible clathrin uncoating...
  55. Maurer M, Cooper J. The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J Cell Sci. 2006;119:4235-46 pubmed
  56. Shimada A, Niwa H, Tsujita K, Suetsugu S, Nitta K, Hanawa Suetsugu K, et al. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell. 2007;129:761-72 pubmed
    ..Furthermore, FBP17 is recruited to clathrin-coated pits in the late stage of CME, indicating its physiological role...
  57. McMahon H, Mills I. COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr Opin Cell Biol. 2004;16:379-91 pubmed
    ..These themes point to the way in which evolutionarily conserved features underpin these diverse pathways...
  58. FOLSCH H, Ohno H, Bonifacino J, Mellman I. A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell. 1999;99:189-98 pubmed
    ..We conclude that basolateral sorting is mediated by an epithelial cell-specific version of the AP-1 complex containing mu1B...
  59. Kirchhausen T. Adaptors for clathrin-mediated traffic. Annu Rev Cell Dev Biol. 1999;15:705-32 pubmed
    ..This review focuses on the most recent advances dealing with the molecular basis for sorting by clathrin adaptors...
  60. Rappoport J, Simon S. Endocytic trafficking of activated EGFR is AP-2 dependent and occurs through preformed clathrin spots. J Cell Sci. 2009;122:1301-5 pubmed publisher
    ..Using imaging techniques to show the endocytic sorting of activated EGFR for the first time in live cells, these studies suggest a refinement of the model for EGFR entry...
  61. Saffarian S, Cocucci E, Kirchhausen T. Distinct dynamics of endocytic clathrin-coated pits and coated plaques. PLoS Biol. 2009;7:e1000191 pubmed publisher
  62. Chen W, Goldstein J, Brown M. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem. 1990;265:3116-23 pubmed
    ..This occurrence is much more frequent than would be expected by chance alone. The possibility of a conditional role for the NPXY sequence in ligand-independent internalization of these proteins is discussed...
  63. Garrett W, Chen L, Kroschewski R, Ebersold M, Turley S, Trombetta S, et al. Developmental control of endocytosis in dendritic cells by Cdc42. Cell. 2000;102:325-34 pubmed
    ..DCs regulate endogenous levels of Cdc42-GTP with activated Cdc42 detectable only in immature cells. We conclude that DCs developmentally regulate endocytosis at least in part by controlling levels of activated Cdc42...