Introduction to the Mobile Receptor Hypothesis

  • David A. Jans
Part of the Molecular Biology Intelligence Unit book series (MBIU)


The idea that proteins float freely within the lipid bilayer of biological membranes gained initial impetus through the formulation of the “fluid mosaic” model in the early 1970s.1 Based on electron microscopy and freeze-fracture analysis as well as a number of other studies, the structure of biological membranes was purported to be and is still believed to be as shown in Figure 1.1: “dissolved” proteins float within the “sea” of membrane lipid. This includes integral membrane proteins, that is, proteins that completely traverse the lipid bilayer sometimes more than once such as membrane receptors, as well as peripheral membrane proteins such as the guanosine-triphosphate (GTP) binding protein (“G-protein”) subunits and cell-cell recognition molecules such as LFA-2 (lymphocyte function-associated antigen-2), which are only associated with the membrane and do not traverse it. They are linked to the lipid bilayer through a variety of covalent modifications, such as glycosyl phosphatidylinositol anchors, myristoyl and palmitoyl fatty acid linkages, etc.


Adenylate Cyclase Cholera Toxin Lateral Movement Adenylate Cyclase System Mobile Receptor 
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  1. 1.
    Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972; 175 (23): 720–731.PubMedCrossRefGoogle Scholar
  2. 2.
    Raff MC, De Petris S. Movement of lymphocyte surface antigens and receptors: the fluid nature of the lymphocyte plasma membrane and its immunological significance. Fed Proc 1973; 32 (1): 48–54.PubMedGoogle Scholar
  3. 3.
    Frye CD, Edidin M. The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons. J Cell Sci 1970; 7 (2): 313–335.Google Scholar
  4. 4.
    Cuatrecasas P. Membrane receptors. Annu Rev Biochem 1974; 43: 169–214.PubMedCrossRefGoogle Scholar
  5. 5.
    Jacobs S Cuatrecasas P. The mobile receptor hypothesis and “cooperativity” of hormone binding. Application to insulin. Biochim Biophys Acta. 1976; 433 (3): 482–495.PubMedCrossRefGoogle Scholar
  6. 6.
    Gitler C. Plasticity of biological membranes. Annu Rev Biophys Bioeng 1972; 1: 51–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Radda GK. Enzyme and membrane conformation in biochemical control. Biochem J 1971; 122 (4): 385–396.PubMedGoogle Scholar
  8. 8.
    Kahn CR. Membrane receptors for hormones and neurotransmitters. J Cell Biol 1976; 70: 261–286.PubMedCrossRefGoogle Scholar
  9. 9.
    Cassel D, Selinger Z. Mechanism of adenylate activation through the 13-adrenergic receptor: catecholamine-induced displacement of bound GDP by GTP. Proc Natl Acad Sci USA 1978; 75 (9): 4155–4159.PubMedCrossRefGoogle Scholar
  10. 10.
    Craig SW, Cuatrecasas P. Mobility of cholera toxin receptors on rat lymphocyte membranes. Proc Natl Acad Sci USA 1975; 72 (10): 3844–3848.PubMedCrossRefGoogle Scholar
  11. 11.
    Bennett V, Cuatrecasas P. Mechanism of activation of adenylate cyclase by Vibrio cholerae enterotoxin. J Memb Biol 1975; 22 (1–2): 29–52.CrossRefGoogle Scholar
  12. 12.
    Sahyoun N, Cuatrecasas P. Mechanism of activation of adenylate cyclase by cholera toxin. Proc Natl Acad Sci USA 1975; 72 (9): 3438–3442.PubMedCrossRefGoogle Scholar
  13. 13.
    Bennett V, O’Keefe E, Cuatrecasas P. Mechanism of action of cholera toxin and the mobile receptor theory of hormone receptor-adenylate cyclase interactions. Proc Natl Acad Sci USA 1975; 72 (1): 33–37.PubMedCrossRefGoogle Scholar
  14. 14.
    Neer EJ. The size of adenylate cyclase. J Biol Chem 1974; 249 (20): 6527–6531.PubMedGoogle Scholar
  15. 15.
    Craig SW, Cuatrecasas P. Immunological probes into the mechanism of cholera toxin action. Immunol Commun 1976; 5 (5): 387–400.PubMedGoogle Scholar
  16. 16.
    Freychet P, Laudat, MH; Laudat G et al. Impairment of insulin binding to the fat cell membrane in the obese hypoglycemic mouse. FEBS Lett 1972; 25: 339–342.PubMedCrossRefGoogle Scholar
  17. 17.
    Kono T, Barham FW. Effects of insulin on the levels of adenosine 3’:5’-monophosphate and lipolysis in isolated rat epididymal fat cells. J Biol Chem 1973; 248 (21): 7417–7426.PubMedGoogle Scholar
  18. 18.
    Megyesi K, Kahn CR, Roth J et al. The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. J Biol Chem 1975; 250 (23): 8990–8996.PubMedGoogle Scholar
  19. 19.
    Kono T, Barham FW. The relationship between the insulin-binding capacity of fat cells and the cellular response to insulin. Studies with intact and trypsintreated fat cells. J Biol Chem 1971; 246 (20): 6210–6216.PubMedGoogle Scholar
  20. 20.
    Huhtaniemi IT, Clayton RN, Catt KJ. Gonadotropin binding and Leydig cell activation in the rat testis in vivo. Endocrinology 1982; 111 (3): 982–987.PubMedCrossRefGoogle Scholar
  21. 21.
    Goldfine ID, Gardner JD, Neville DM Jr. Insulin action in isolated rat thymocytes. I. Binding of 125 I-insulin and stimulation of alpha-aminoisobutyric acid transport. J Biol Chem 1972; 247 (21): 6919–6926.PubMedGoogle Scholar
  22. 22.
    Hollenberg MD, Cuatrecasas P. Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake. J Biol Chem 1975; 250: 3845–3853.PubMedGoogle Scholar
  23. 23.
    Wicks WD. Induction of hepatic enzymes by adenosine 3’,5’-monophosphate in organ culture. J Biol Chem 1969; 244: 3941–3950.PubMedGoogle Scholar
  24. 24.
    Hsueh AJ, Dufau ML, Catt KJ. Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3’:5’-cyclic AMP and testosterone responses. Proc Natl Acad Sci USA 1977; 74 (2): 592–595.PubMedCrossRefGoogle Scholar
  25. 25.
    Moyle WR, Lee EY, Bahl OP et al. New method of quantifying ligand binding based on measurement of an induced response. Am J Physiol 1977; 232 (3): E274 - E285.PubMedGoogle Scholar
  26. 26.
    Orly J, Schramm M. Fatty acids as modulators of membrane functions; catecholamine-activated adenylate cyclase of the turkey erythrocyte. Proc Natl Acad Sci USA 1975; 72: 3433–3437.PubMedCrossRefGoogle Scholar
  27. 27.
    Brandt DR, Ross EM. Catecholamine-stimulated GTPase cycle; multiple sites of regulation by ß-adrenergic recceptor and Mgt’ studied in reconstituted receptor-G, vesicles. J Biol Chem 1986; 261: 1656–1664.PubMedGoogle Scholar
  28. 28.
    De Haen C. The non-stoichiometric floating receptor model for hormone sensitive adenylyl cyclase. J Theor Biol 1976; 58: 383–400.PubMedCrossRefGoogle Scholar
  29. 29.
    Perkins JP. Adenyl cyclase. Adv Cyclic Nucleotide Res 1973; 3: 1–64.PubMedGoogle Scholar
  30. 30.
    Jans DA. The mobile receptor hypothesis revisited: a mechanistic role for hormone receptor lateral mobility in signal transduction. Biochim Biophys Acta 1992; 1113: 271–276.PubMedCrossRefGoogle Scholar
  31. 31.
    Jans DA, Pavo I. A mechanistic role for polypeptide hormone receptor lateral mobility in signal transduction. Amino Acids 1995; 9: 93–109.Google Scholar
  32. 32.
    Helmreich EJM, Elson EL. Protein and lipid mobility. Adv in Cyclic Nucleotide and Prot Phosphor Res 1984; 18: 1–62.Google Scholar
  33. 33.
    Peters R. Translational diffusion in the plasma membrane of single cells as studied by fluorescence microphotolysis. Cell Biol Int Rep 1981; 5 (8): 733–760.PubMedCrossRefGoogle Scholar
  34. 34.
    Jans DA. Nuclear signaling pathways for extracellular ligands and their membrane-integral receptors? FASEB J 1994; 8: 841–847.PubMedGoogle Scholar
  35. 35.
    Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988; 13: 443–447.PubMedCrossRefGoogle Scholar
  36. 36.
    Schlessinger J. The epidermal growth factor receptor as a multifunctional allosteric protein. Biochemistry 1989; 27: 3119–3123.CrossRefGoogle Scholar
  37. 37.
    Jans DA, Peters R, Zsigo J et al. The adenylate cyclase-coupled vasopressin V2-receptor is highly laterally mobile in membranes of LLC-PK, renal epithelial cells at physiological temperature. EMBO J 1989; 8 (9): 2431–2438.Google Scholar
  38. 38.
    Jans DA, Peters R, Fahrenholz F. Lateral mobility of the phospholipase-C-activating vasopressin V1-type receptor in A7r5 smooth muscle cells: a comparison with the adenylate cyclase-coupled V2-receptor. EMBO J 1990; 9 (9): 2693–2699.PubMedGoogle Scholar
  39. 39.
    Jans DA, Peters R, Jans P et al. Ammonium chloride affects receptor number and lateral mobility of the vasopressin V2-type receptor in the plasma membrane of LLC-PK, renal epithelial cells: role of the cytoskeleton. Exper Cell Res 1990; 191: 121–128.CrossRefGoogle Scholar
  40. 40.
    Jans DA, Peters R, Jans P et al. Vasopressin V2-receptor mobile fraction and ligand-dependent adenylate cyclase-activity are directly correlated in LLC-PK, renal epithelial cells. J Cell Biol 1991; 114 (1): 53–60.PubMedCrossRefGoogle Scholar
  41. 41.
    Pavo I, Jans DA, Peters R et al. A vasopressin antagonist that binds to the V2-receptor of LLC-PK, renal epithelial cells is highly laterally mobile but does not effect ligand-induced receptor immobilization. Biochim Biophys Acta 1994; 1223: 240–246.PubMedCrossRefGoogle Scholar
  42. 42.
    Zakharova OM, Rosenkranz AA, Sobolev AS. Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory. Biochim Biophys Acta 1995; 1236: 177–184.PubMedCrossRefGoogle Scholar
  43. 43.
    Taga T, Kishimoto T. Cytokine receptors and signal transduction. FASEB J 1992; 6: 3387–3396.PubMedGoogle Scholar
  44. 44.
    Stomski FC, Sun Q, Bagley CJ et al. Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha-and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding. Mol Cell Biol 1996; 16 (6): 3035–3046.PubMedGoogle Scholar
  45. 45.
    Posner RG, Subramanian K, Goldstein B et al. Simultaneous cross-linking by two nontriggering bivalent ligands causes synergistic signaling of IgE Fc epsilon RI complexes. J Immunol 1995; 155 (7): 3601–3609.PubMedGoogle Scholar
  46. 46.
    Menon AK, Holowka D, Webb WW et al. Clustering, mobility, and triggering activity of small oligomers of immunoglobulin E on rat basophilic leukemia cells. J Cell Biol 1986; 102: 534–540.Google Scholar
  47. 47.
    Menon AK, Holowka D, Webb WW et al. Cross-linking of receptor-bound IgE to aggregates larger than dimers leads to rapid immobilization. J Cell Biol 1986; 102: 541–550.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu SJ, Hahn WC, Bierer BE et al. Intracellular mediators regulate CD2 lateral diffusion and cytoplasmic Cat` mobilization upon CD2-mediated T cell activation. Biophys J 1995; 68 (2): 459–470.PubMedCrossRefGoogle Scholar
  49. 49.
    Chan PY, Lawrence MB, Dustin ML et al. Influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2. J Cell Biol 1991; 115 (1): 245–255.PubMedCrossRefGoogle Scholar
  50. 50.
    Duband J-L, Nuckolls GH, Ishihara A et al. Fibronectin receptor exhibits high lateral mobility in embryonic locomoting cells but is immobile in focal contacts and fibrillar streaks in stationary cells. J Cell Biol 1988; 107: 1385–1396PubMedCrossRefGoogle Scholar

Copyright information

© R.G. Landes Company 1997

Authors and Affiliations

  • David A. Jans
    • 1
  1. 1.John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia

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