receptor aggregation


Summary: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.

Top Publications

  1. Apel E, Glass D, Moscoso L, Yancopoulos G, Sanes J. Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold. Neuron. 1997;18:623-35 pubmed
    ..This signaling requires the kinase domain of MuSK, but not its ectodomain. Thus, MuSK may interact with rapsyn in multiple ways to play both structural and signaling roles in agrin-induced differentiation. ..
  2. Brandon E, Lin W, D Amour K, Pizzo D, Dominguez B, Sugiura Y, et al. Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice. J Neurosci. 2003;23:539-49 pubmed
    ..These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses. ..
  3. Khan A, Bose C, Yam L, Soloski M, Rupp F. Physiological regulation of the immunological synapse by agrin. Science. 2001;292:1681-6 pubmed
    ..Our data show that agrin induces the aggregation of signaling proteins and the creation of signaling domains in both immune and nervous systems through a common lipid raft pathway. ..
  4. Kremyanskaya M, Monroe J. Ig-independent Ig beta expression on the surface of B lymphocytes after B cell receptor aggregation. J Immunol. 2005;174:1501-6 pubmed
    ..These results suggest that sIg and Igbeta may function independently following the initial stages of signal transduction. ..
  5. Kammermeier P, Xiao B, Tu J, Worley P, Ikeda S. Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels. J Neurosci. 2000;20:7238-45 pubmed
    ..Thus, Homer may regulate the magnitude and predominate signaling output of group I mGluRs. ..
  6. Weston C, Yee B, Hod E, Prives J. Agrin-induced acetylcholine receptor clustering is mediated by the small guanosine triphosphatases Rac and Cdc42. J Cell Biol. 2000;150:205-12 pubmed
  7. Grow W, Gordon H. Sialic acid inhibits agrin signaling in C2 myotubes. Cell Tissue Res. 2000;299:273-9 pubmed
  8. Tolar P, Sohn H, Liu W, Pierce S. The molecular assembly and organization of signaling active B-cell receptor oligomers. Immunol Rev. 2009;232:34-41 pubmed publisher
  9. Lee K, Dinner A, Tu C, Campi G, Raychaudhuri S, Varma R, et al. The immunological synapse balances T cell receptor signaling and degradation. Science. 2003;302:1218-22 pubmed
    ..We use in vitro and in silico experiments to determine that the immunological synapse acts as a type of adaptive controller that both boosts T cell receptor triggering and attenuates strong signals. ..

More Information


  1. Miyamoto S, Teramoto H, Gutkind J, Yamada K. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J Cell Biol. 1996;135:1633-42 pubmed
  2. Sandilands G, Wilson M, Huser C, Jolly L, Sands W, McSharry C. Were monocytes responsible for initiating the cytokine storm in the TGN1412 clinical trial tragedy?. Clin Exp Immunol. 2010;162:516-27 pubmed publisher
    ..Furthermore, we propose that a multimeric antibody array may have formed in vivo on the vascular endothelium via an interaction between TGN1412 and CD64 (Fc?RI), and we provide some evidence in support of this hypothesis. ..
  3. Krawczyk C, Penninger J. Molecular controls of antigen receptor clustering and autoimmunity. Trends Cell Biol. 2001;11:212-20 pubmed
    ..This review discusses the role of Cbl-b, Vav and WASP in the regulation of SMAC formation and the implications for the maintenance of tolerance and the development of autoimmunity. ..
  4. Algeciras Schimnich A, Shen L, Barnhart B, Murmann A, Burkhardt J, Peter M. Molecular ordering of the initial signaling events of CD95. Mol Cell Biol. 2002;22:207-20 pubmed
    ..The data indicate that the signal initiation by CD95 is a complex process actively regulated at various levels, providing a number of new drug targets to specifically modulate CD95 signaling. ..
  5. Kunkel D, Lee L, Stollberg J. Ultrastructure of acetylcholine receptor aggregates parallels mechanisms of aggregation. BMC Neurosci. 2001;2:19 pubmed
    ..While a major physiological signal for receptor aggregation (agrin) is known, the mechanism(s) by which muscle cells respond to this and other stimuli have yet to be ..
  6. Lee K, Holdorf A, Dustin M, Chan A, Allen P, Shaw A. T cell receptor signaling precedes immunological synapse formation. Science. 2002;295:1539-42 pubmed
    ..These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation. ..
  7. Denzer A, Brandenberger R, Gesemann M, Chiquet M, Ruegg M. Agrin binds to the nerve-muscle basal lamina via laminin. J Cell Biol. 1997;137:671-83 pubmed
    ..These data strongly suggest that binding of agrin to laminin provides the basis of its localization to synaptic basal lamina and other basement membranes. ..
  8. Gonzalez M, Ruggiero F, Chang Q, Shi Y, Rich M, Kraner S, et al. Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Neuron. 1999;24:567-83 pubmed
    ..These results demonstrate a novel role for neurotrophin signaling through TrkB receptors on muscle fibers in the ongoing maintenance of postsynaptic AChR regions. ..
  9. Buensuceso C, de Virgilio M, Shattil S. Detection of integrin alpha IIbbeta 3 clustering in living cells. J Biol Chem. 2003;278:15217-24 pubmed
    ..These studies in living cells establish that alpha(IIb)beta(3) clustering is modulated by fibrinogen and actin dynamics. More broadly, they should facilitate investigations of the mechanisms and consequences of integrin clustering. ..
  10. Dai Z, Peng H. A role of tyrosine phosphatase in acetylcholine receptor cluster dispersal and formation. J Cell Biol. 1998;141:1613-24 pubmed
  11. Standeven L, Carlin L, Borszcz P, Davis D, Burshtyn D. The actin cytoskeleton controls the efficiency of killer Ig-like receptor accumulation at inhibitory NK cell immune synapses. J Immunol. 2004;173:5617-25 pubmed
    ..Collectively, these data suggest that the actin cytoskeleton and the cytoplasmic tail of KIR regulate the efficiency by which KIR accumulates at inhibitory NK cell synapses. ..
  12. Li R, Mitra N, Gratkowski H, Vilaire G, Litvinov R, Nagasami C, et al. Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations. Science. 2003;300:795-8 pubmed
    ..These results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation. They also suggest a structural basis for the coincidence of integrin activation and clustering. ..
  13. Mittaud P, Camilleri A, Willmann R, Erb Vögtli S, Burden S, Fuhrer C. A single pulse of agrin triggers a pathway that acts to cluster acetylcholine receptors. Mol Cell Biol. 2004;24:7841-54 pubmed
    ..Second, a kinase mechanism rapidly activated by agrin acts thereafter autonomously in agrin's absence to further increase MuSK phosphorylation and cluster AChRs. ..
  14. Bezakova G, Lømo T. Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers. J Cell Biol. 2001;153:1453-63 pubmed
    ..The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin. ..
  15. Faure M, Barber D, Takahashi S, Jin T, Long E. Spontaneous clustering and tyrosine phosphorylation of NK cell inhibitory receptor induced by ligand binding. J Immunol. 2003;170:6107-14 pubmed
    ..The unique property of KIR to become phosphorylated in the absence of adhesion and of actin cytoskeleton rearrangement explains how KIR can efficiently block early activation signals during NK-target cell contacts. ..
  16. Lin W, Dominguez B, Yang J, Aryal P, Brandon E, Gage F, et al. Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism. Neuron. 2005;46:569-79 pubmed
    ..Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism. ..
  17. Molfetta R, Peruzzi G, Santoni A, Paolini R. Negative signals from FcepsilonRI engagement attenuate mast cell functions. Arch Immunol Ther Exp (Warsz). 2007;55:219-29 pubmed
    ..Similar mechanisms are employed by other receptors expressed by immune cells, such as T cell and B cell receptors, pointing to a general concept in negative immunoreceptor signaling. ..
  18. Montanaro F, Gee S, Jacobson C, Lindenbaum M, Froehner S, Carbonetto S. Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway. J Neurosci. 1998;18:1250-60 pubmed
    ..We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism. ..
  19. Zhang B, Luo S, Wang Q, Suzuki T, Xiong W, Mei L. LRP4 serves as a coreceptor of agrin. Neuron. 2008;60:285-97 pubmed publisher
    ..These observations indicate that LRP4 is a coreceptor of agrin that is necessary for MuSK signaling and AChR clustering and identify a potential target protein whose mutation and/or autoimmunization may cause muscular dystrophies. ..
  20. Bezakova G, Helm J, Francolini M, Lømo T. Effects of purified recombinant neural and muscle agrin on skeletal muscle fibers in vivo. J Cell Biol. 2001;153:1441-52 pubmed
    ..Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo. ..
  21. Madhavan R, Zhao X, Ruegg M, Peng H. Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor clustering. Mol Cell Neurosci. 2005;28:403-16 pubmed
    ..Our results suggest that muscle tyrosine phosphatases tightly regulate MuSK activation and signaling and support a novel role of Shp2 in MuSK-dependent AChR clustering. ..
  22. Schweitzer Stenner R, Pecht I. Death of a dogma or enforcing the artificial: monomeric IgE binding may initiate mast cell response by inducing its receptor aggregation. J Immunol. 2005;174:4461-4 pubmed
    ..Hence, we hypothesize that the reported response to mIgE binding is a result of such an Fc epsilon RI-IgE induced aggregation. ..
  23. Krawczyk C, Bachmaier K, Sasaki T, Jones R, Snapper S, Bouchard D, et al. Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells. Immunity. 2000;13:463-73 pubmed
    ..Thus, Cbl-b functions as a negative regulator of receptor clustering and raft aggregation in T cells. ..
  24. Meier T, Hauser D, Chiquet M, Landmann L, Ruegg M, Brenner H. Neural agrin induces ectopic postsynaptic specializations in innervated muscle fibers. J Neurosci. 1997;17:6534-44 pubmed
    ..Thus, a motor neuron-specific agrin isoform is sufficient to induce a full ectopic postsynaptic apparatus in muscle fibers kept electrically active at their original endplate sites. ..
  25. Megeath L, Kirber M, Hopf C, Hoch W, Fallon J. Calcium-dependent maintenance of agrin-induced postsynaptic specializations. Neuroscience. 2003;122:659-68 pubmed
    ..These findings suggest an avenue by which postsynaptic stability can be regulated by modification of intracellular signaling pathways that are distinct from those used during synapse formation. ..
  26. Smith C, Mittaud P, Prescott E, Fuhrer C, Burden S. Src, Fyn, and Yes are not required for neuromuscular synapse formation but are necessary for stabilization of agrin-induced clusters of acetylcholine receptors. J Neurosci. 2001;21:3151-60 pubmed
    ..These data show that the stabilization of agrin-induced AChR clusters requires Src and Fyn and suggest that the adaptor activities, rather than the kinase activities, of these kinases are essential for this stabilization. ..
  27. Gruener R, Roberts R, Reitstetter R. Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight. Biol Sci Space. 1994;8:79-93 pubmed
    ..Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly ..
  28. Villunger A, Huang D, Holler N, Tschopp J, Strasser A. Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve DAXX, RIP, or RAIDD. J Immunol. 2000;165:1337-43 pubmed
  29. Mi R, Tang X, Sutter R, Xu D, Worley P, O Brien R. Differing mechanisms for glutamate receptor aggregation on dendritic spines and shafts in cultured hippocampal neurons. J Neurosci. 2002;22:7606-16 pubmed
    ..Furthermore, our data suggest the existence of a novel molecule(s), capable of forming excitatory synapses on dendritic spines. ..
  30. Lin S, Landmann L, Ruegg M, Brenner H. The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formation. J Neurosci. 2008;28:3333-40 pubmed publisher
    ..A model is proposed that explains either the neurocentric or the myocentric mode of NMJ formation depending on a balance between the levels of MuSK expression and the availability of nerve-released agrin. ..
  31. Diakonova M, Payrastre B, van Velzen A, Hage W, van Bergen en Henegouwen P, Boonstra J, et al. Epidermal growth factor induces rapid and transient association of phospholipase C-gamma 1 with EGF-receptor and filamentous actin at membrane ruffles of A431 cells. J Cell Sci. 1995;108 ( Pt 6):2499-509 pubmed
  32. Tsim K, Ruegg M, Escher G, Kroger S, McMahan U. cDNA that encodes active agrin. Neuron. 1992;8:677-89 pubmed
  33. Benhamou M, Ryba N, Kihara H, Nishikata H, Siraganian R. Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation. J Biol Chem. 1993;268:23318-24 pubmed
    ..Association of p72syk with the tyrosine phosphorylated Fc epsilon RI gamma chain was detected only after receptor aggregation. We previously demonstrated that aggregation of the Fc epsilon RI on mast cells results in the tyrosine ..
  34. Gee S, Montanaro F, Lindenbaum M, Carbonetto S. Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor. Cell. 1994;77:675-86 pubmed
    ..Moreover, MAb IIH6 significantly inhibits agrin-induced AChR aggregation on C2 cells. We conclude that dystroglycan-alpha is an agrin-binding protein and part of a dystrophin-receptor complex involved in AChR aggregation. ..
  35. Javaid K, Rahman A, Anwar K, Frey R, Minshall R, Malik A. Tumor necrosis factor-alpha induces early-onset endothelial adhesivity by protein kinase Czeta-dependent activation of intercellular adhesion molecule-1. Circ Res. 2003;92:1089-97 pubmed
    ..The rapid ICAM-1 expression represents a novel mechanism for promoting the stable adhesion of PMN to endothelial cells that is needed to facilitate the early-onset transendothelial migration of PMN. ..
  36. Zhu J, Yu D, Zeng X, Zhou K, Zhan X. Receptor-mediated endocytosis involves tyrosine phosphorylation of cortactin. J Biol Chem. 2007;282:16086-94 pubmed
    ..On the other hand, Src-treated dynamin-2 had no effect on its interaction with cortactin. These data indicate that Src kinase is implicated in clathrin-mediated endocytosis by phosphorylation of cortactin. ..
  37. Reiss J, Gross Hardt S, Christensen E, Schmidt P, Mendel R, Schwarz G. A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Am J Hum Genet. 2001;68:208-13 pubmed
    ..Biochemical studies of the patient's fibroblasts demonstrate that gephyrin catalyzes the insertion of molybdenum into molybdopterin and suggest that this novel form of MoCo deficiency might be curable by molybdate supplementation. ..
  38. Szabo Z, Obermair G, Cooper C, Zamponi G, Flucher B. Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons. Eur J Neurosci. 2006;24:709-18 pubmed
    ..The unique targeting properties of the splice variants lacking the synprint site are suggestive of specific functions of these calcium channels apart from activating fast synaptic transmission. ..
  39. Xia J, Zhang X, Staudinger J, Huganir R. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron. 1999;22:179-87 pubmed
    ..These results suggest that PICK1 may play an important role in the modulation of synaptic transmission by regulating the synaptic targeting of AMPA receptors. ..
  40. Renganathan M, Messi M, Delbono O. Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle. J Membr Biol. 1997;157:247-53 pubmed
  41. Perez J, Khatri L, Chang C, Srivastava S, Osten P, Ziff E. PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci. 2001;21:5417-28 pubmed
  42. Ngo S, Balke C, Phillips W, Noakes P. Neuregulin potentiates agrin-induced acetylcholine receptor clustering in myotubes. Neuroreport. 2004;15:2501-5 pubmed
    ..When myotubes were treated for 4 h with 100 pM agrin, HRG-beta1 augmented AChR cluster numbers by 2-fold compared to myotubes treated with 100 pM agrin alone. Thus, HRG-beta1 can potentiate agrin-induced AChR clustering. ..
  43. Chen E, Bartlett M, Loo T, Clarke D. The DeltaF508 mutation disrupts packing of the transmembrane segments of the cystic fibrosis transmembrane conductance regulator. J Biol Chem. 2004;279:39620-7 pubmed
    ..Therefore, a potential target to correct folding defects in the DeltaF508 mutant of CFTR is to identify compounds that promote correct folding of the TM domains. ..
  44. Hat B, Kazmierczak B, Lipniacki T. B cell activation triggered by the formation of the small receptor cluster: a computational study. PLoS Comput Biol. 2011;7:e1002197 pubmed publisher
    ..The model provides a plausible mechanism of B cells activation due to the formation of small receptors clusters collocalized by binding of polyvalent antigens or arising during the immune synapse formation. ..
  45. Essrich C, Lorez M, Benson J, Fritschy J, Luscher B. Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci. 1998;1:563-71 pubmed
    ..The gamma 2 subunit and gephyrin are thus interdependent components of the same synaptic complex that is critical for postsynaptic clustering of abundant subtypes of GABAA receptors in vivo. ..
  46. Fukada M, Fujikawa A, Chow J, Ikematsu S, Sakuma S, Noda M. Protein tyrosine phosphatase receptor type Z is inactivated by ligand-induced oligomerization. FEBS Lett. 2006;580:4051-6 pubmed
  47. Neumann F, Bittcher G, Annies M, Schumacher B, Kroger S, Ruegg M. An alternative amino-terminus expressed in the central nervous system converts agrin to a type II transmembrane protein. Mol Cell Neurosci. 2001;17:208-25 pubmed
    ..Agrin transcripts encoding this form are enriched in the embryonic brain, particularly in neurons. To our knowledge, this is the first example of a molecule that is synthesized both as a basal lamina and a plasma membrane protein. ..
  48. Rabiet M, Huet E, Boulay F. Complement component 5a receptor oligomerization and homologous receptor down-regulation. J Biol Chem. 2008;283:31038-46 pubmed publisher
    ..The existence and functional implication of di(oligo)mer formation may be important for an accurate C5aR down-regulation in pathological conditions. ..
  49. Tsim K, Leung K, Mok K, Chen V, Zhu K, Zhu J, et al. Expression and Localization of PRiMA-linked globular form acetylcholinesterase in vertebrate neuromuscular junctions. J Mol Neurosci. 2010;40:40-6 pubmed publisher
    ..These findings suggest that the restricted localization of PRiMA-linked G4 AChE at the nmjs could be contributed by the pre-synaptic motor neuron and/or the post-synaptic muscle fiber. ..
  50. Xu R, Povlsen G, Soroka V, Bock E, Berezin V. A peptide antagonist of the ErbB1 receptor inhibits receptor activation, tumor cell growth and migration in vitro and xenograft tumor growth in vivo. Cell Oncol. 2010;32:259-74 pubmed publisher
    ..Moreover, the here described biological effects of Inherbin3 suggest that peptide-based targeting of ErbB receptor dimerization is a promising anti-cancer therapeutic strategy. ..
  51. Sun H, Chen X, Chen X, Liu J, Ma L, Wu H, et al. PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and Depolymerization. J Immunol. 2017;199:1817-1826 pubmed publisher
    ..Collectively, our results show a new function for PALLD as a crucial regulator of the early phase of phagocytosis by elaborating dynamic actin polymerization and depolymerization. ..
  52. van de Poll M, van Rotterdam W, Gadellaa M, Jacobs Oomen S, van Zoelen E. Ligand depletion negatively controls the mitogenic activity of epidermal growth factor. Exp Cell Res. 2005;304:630-41 pubmed
    ..No such dependence on the incubation volume was observed for EGF activity on cells with low ErbB1 expression levels and on cells for which EGF is growth inhibitory. ..
  53. Dalskov S, Immerdal L, Niels Christiansen L, Hansen G, Schousboe A, Danielsen E. Lipid raft localization of GABA A receptor and Na+, K+-ATPase in discrete microdomain clusters in rat cerebellar granule cells. Neurochem Int. 2005;46:489-99 pubmed
    ..By providing an ordered membrane microenvironment, lipid rafts may contribute to the clustering of the GABA(A) receptor and the Na(+), K(+)-ATPase at distinct functional locations on the cell surface. ..