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. 2000 Jan;78(1):125–135. doi: 10.1016/S0006-3495(00)76579-9

Regulation of protein mobility in cell membranes: a dynamic corral model.

D M Leitner 1, F L Brown 1, K R Wilson 1
PMCID: PMC1300624  PMID: 10620280

Abstract

We analyze a two-state stochastic corral model for regulation of protein diffusion in a cell membrane. This model could mimic control of protein transport in the membrane by the cytoskeleton. The dynamic corral acts as a gate which when open permits an otherwise trapped protein to escape to a neighboring corral in the cytoskeletal network. We solve for the escape rate over a wide range of parameters of the model, and compare these results with Monte Carlo simulations. Upon introducing measured values of the model parameters for Band 3 in erythrocyte membranes, we are able to estimate the value for one unknown parameter, the average rate at which the corral closes. The ratio of calculated closing rate to measured opening rate is roughly 100:1, consistent with a gating mechanism whereby protein mobility is regulated by dissociation and reassociation of segments of the cytoskeletal network.

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Selected References

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  1. Axelrod D. Lateral motion of membrane proteins and biological function. J Membr Biol. 1983;75(1):1–10. doi: 10.1007/BF01870794. [DOI] [PubMed] [Google Scholar]
  2. Berg H. C., Purcell E. M. Physics of chemoreception. Biophys J. 1977 Nov;20(2):193–219. doi: 10.1016/S0006-3495(77)85544-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boal D. H., Boey S. K. Barrier-free paths of directed protein motion in the erythrocyte plasma membrane. Biophys J. 1995 Aug;69(2):372–379. doi: 10.1016/S0006-3495(95)79909-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boal D. H. Computer simulation of a model network for the erythrocyte cytoskeleton. Biophys J. 1994 Aug;67(2):521–529. doi: 10.1016/S0006-3495(94)80511-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherry R. J. Rotational and lateral diffusion of membrane proteins. Biochim Biophys Acta. 1979 Dec 20;559(4):289–327. doi: 10.1016/0304-4157(79)90009-1. [DOI] [PubMed] [Google Scholar]
  6. Corbett J. D., Agre P., Palek J., Golan D. E. Differential control of band 3 lateral and rotational mobility in intact red cells. J Clin Invest. 1994 Aug;94(2):683–688. doi: 10.1172/JCI117385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Druger SD, Ratner MA, Nitzan A. Generalized hopping model for frequency-dependent transport in a dynamically disordered medium, with applications to polymer solid electrolytes. Phys Rev B Condens Matter. 1985 Mar 15;31(6):3939–3947. doi: 10.1103/physrevb.31.3939. [DOI] [PubMed] [Google Scholar]
  8. Edidin M., Kuo S. C., Sheetz M. P. Lateral movements of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science. 1991 Nov 29;254(5036):1379–1382. doi: 10.1126/science.1835798. [DOI] [PubMed] [Google Scholar]
  9. Fleming T. P. Trapped by a skeleton--the maintenance of epithelial membrane domains. Bioessays. 1987 Oct;7(4):179–181. doi: 10.1002/bies.950070410. [DOI] [PubMed] [Google Scholar]
  10. Harrison AK, Zwanzig R. Transport on a dynamically disordered lattice. Phys Rev A Gen Phys. 1985 Aug;32(2):1072–1075. doi: 10.1103/physreva.32.1072. [DOI] [PubMed] [Google Scholar]
  11. Jacobson K., Elson E., Koppel D., Webb W. Fluorescence photobleaching in cell biology. Nature. 1982 Jan 28;295(5847):283–284. doi: 10.1038/295283a0. [DOI] [PubMed] [Google Scholar]
  12. Jacobson K., Sheets E. D., Simson R. Revisiting the fluid mosaic model of membranes. Science. 1995 Jun 9;268(5216):1441–1442. doi: 10.1126/science.7770769. [DOI] [PubMed] [Google Scholar]
  13. Koppel D. E., Sheetz M. P., Schindler M. Matrix control of protein diffusion in biological membranes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3576–3580. doi: 10.1073/pnas.78.6.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kusumi A., Sako Y. Cell surface organization by the membrane skeleton. Curr Opin Cell Biol. 1996 Aug;8(4):566–574. doi: 10.1016/s0955-0674(96)80036-6. [DOI] [PubMed] [Google Scholar]
  15. Kusumi A., Sako Y., Fujiwara T., Tomishige M. Application of laser tweezers to studies of the fences and tethers of the membrane skeleton that regulate the movements of plasma membrane proteins. Methods Cell Biol. 1998;55:173–194. doi: 10.1016/s0091-679x(08)60408-2. [DOI] [PubMed] [Google Scholar]
  16. Kusumi A., Sako Y., Yamamoto M. Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys J. 1993 Nov;65(5):2021–2040. doi: 10.1016/S0006-3495(93)81253-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liu S. C., Palek J., Prchal J., Castleberry R. P. Altered spectrin dimer-dimer association and instability of erythrocyte membrane skeletons in hereditary pyropoikilocytosis. J Clin Invest. 1981 Sep;68(3):597–605. doi: 10.1172/JCI110293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McCammon J. A., Northrup S. H. Gated binding of ligands to proteins. Nature. 1981 Sep 24;293(5830):316–317. doi: 10.1038/293316a0. [DOI] [PubMed] [Google Scholar]
  19. McCloskey M., Poo M. M. Protein diffusion in cell membranes: some biological implications. Int Rev Cytol. 1984;87:19–81. doi: 10.1016/s0074-7696(08)62439-0. [DOI] [PubMed] [Google Scholar]
  20. Palek J., Lux S. E. Red cell membrane skeletal defects in hereditary and acquired hemolytic anemias. Semin Hematol. 1983 Jul;20(3):189–224. [PubMed] [Google Scholar]
  21. Peters R. Lateral mobility of proteins and lipids in the red cell membrane and the activation of adenylate cyclase by beta-adrenergic receptors. FEBS Lett. 1988 Jul 4;234(1):1–7. doi: 10.1016/0014-5793(88)81290-0. [DOI] [PubMed] [Google Scholar]
  22. Qian H., Sheetz M. P., Elson E. L. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys J. 1991 Oct;60(4):910–921. doi: 10.1016/S0006-3495(91)82125-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saffman P. G., Delbrück M. Brownian motion in biological membranes. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3111–3113. doi: 10.1073/pnas.72.8.3111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sako Y., Kusumi A. Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. J Cell Biol. 1995 Jun;129(6):1559–1574. doi: 10.1083/jcb.129.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sako Y., Nagafuchi A., Tsukita S., Takeichi M., Kusumi A. Cytoplasmic regulation of the movement of E-cadherin on the free cell surface as studied by optical tweezers and single particle tracking: corralling and tethering by the membrane skeleton. J Cell Biol. 1998 Mar 9;140(5):1227–1240. doi: 10.1083/jcb.140.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saxton M. J., Jacobson K. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct. 1997;26:373–399. doi: 10.1146/annurev.biophys.26.1.373. [DOI] [PubMed] [Google Scholar]
  27. Saxton M. J. Lateral diffusion in an archipelago. Single-particle diffusion. Biophys J. 1993 Jun;64(6):1766–1780. doi: 10.1016/S0006-3495(93)81548-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saxton M. J. Lateral diffusion in an archipelago. The effect of mobile obstacles. Biophys J. 1987 Dec;52(6):989–997. doi: 10.1016/S0006-3495(87)83291-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saxton M. J. Single-particle tracking: effects of corrals. Biophys J. 1995 Aug;69(2):389–398. doi: 10.1016/S0006-3495(95)79911-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Saxton M. J. Single-particle tracking: the distribution of diffusion coefficients. Biophys J. 1997 Apr;72(4):1744–1753. doi: 10.1016/S0006-3495(97)78820-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Saxton M. J. The membrane skeleton of erythrocytes. A percolation model. Biophys J. 1990 Jun;57(6):1167–1177. doi: 10.1016/S0006-3495(90)82636-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Saxton M. J. The membrane skeleton of erythrocytes: models of its effect on lateral diffusion. Int J Biochem. 1990;22(8):801–809. doi: 10.1016/0020-711x(90)90283-9. [DOI] [PubMed] [Google Scholar]
  33. Saxton M. J. The spectrin network as a barrier to lateral diffusion in erythrocytes. A percolation analysis. Biophys J. 1989 Jan;55(1):21–28. doi: 10.1016/S0006-3495(89)82776-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schindler M., Koppel D. E., Sheetz M. P. Modulation of membrane protein lateral mobility by polyphosphates and polyamines. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1457–1461. doi: 10.1073/pnas.77.3.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sheetz M. P. Membrane skeletal dynamics: role in modulation of red cell deformability, mobility of transmembrane proteins, and shape. Semin Hematol. 1983 Jul;20(3):175–188. [PubMed] [Google Scholar]
  36. Sheetz M. P., Schindler M., Koppel D. E. Lateral mobility of integral membrane proteins is increased in spherocytic erythrocytes. Nature. 1980 Jun 12;285(5765):510–511. doi: 10.1038/285510a0. [DOI] [PubMed] [Google Scholar]
  37. Simson R., Sheets E. D., Jacobson K. Detection of temporary lateral confinement of membrane proteins using single-particle tracking analysis. Biophys J. 1995 Sep;69(3):989–993. doi: 10.1016/S0006-3495(95)79972-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  39. Tomishige M., Sako Y., Kusumi A. Regulation mechanism of the lateral diffusion of band 3 in erythrocyte membranes by the membrane skeleton. J Cell Biol. 1998 Aug 24;142(4):989–1000. doi: 10.1083/jcb.142.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tsuji A., Kawasaki K., Ohnishi S., Merkle H., Kusumi A. Regulation of band 3 mobilities in erythrocyte ghost membranes by protein association and cytoskeletal meshwork. Biochemistry. 1988 Sep 20;27(19):7447–7452. doi: 10.1021/bi00419a041. [DOI] [PubMed] [Google Scholar]
  41. Tsuji A., Ohnishi S. Restriction of the lateral motion of band 3 in the erythrocyte membrane by the cytoskeletal network: dependence on spectrin association state. Biochemistry. 1986 Oct 7;25(20):6133–6139. doi: 10.1021/bi00368a045. [DOI] [PubMed] [Google Scholar]
  42. Webb W. W., Barak L. S., Tank D. W., Wu E. S. Molecular mobility on the cell surface. Biochem Soc Symp. 1981;(46):191–205. [PubMed] [Google Scholar]
  43. Winckler B., Forscher P., Mellman I. A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature. 1999 Feb 25;397(6721):698–701. doi: 10.1038/17806. [DOI] [PubMed] [Google Scholar]
  44. Zhang F., Lee G. M., Jacobson K. Protein lateral mobility as a reflection of membrane microstructure. Bioessays. 1993 Sep;15(9):579–588. doi: 10.1002/bies.950150903. [DOI] [PubMed] [Google Scholar]

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