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Reelin is a large extracellular protein involved in several aspects of brain development, such as cell positioning, dendrite growth, synaptic plasticity, and memory, and may be implicated as a susceptibility factor in psychoses (Caviness and Rakic, 1978; Impagnatiello et al., 1998; Liu et al., 2001; Weeber et al., 2002; Jossin, 2004; Beffert et al., 2005; Fatemi, 2005). This wide array of functions indicates that Reelin is able to trigger different intracellular signaling pathways depending on the maturation state or the type of target cell that may express different receptors or intracellular signaling modules. In this chapter, I will review the current state of knowledge on the best established and some other putative partners of the Reelin pathway (Fig. 3.1).

Keywords

Neuronal Migration Lipoprotein Receptor ApoE Receptor Reelin Signaling VLDL Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Andersen, O. M., Benhayon, D., Curran, T., and Willnow, T. E. (2003). Differential binding of ligands to the apolipoprotein E receptor 2. Biochemistry 42:9355-9364.CrossRefPubMedGoogle Scholar
  2. Anton, E. S., Kreidberg, J. A., and Rakic, P. (1999). Distinct functions of alpha3 and alpha(v) integrin receptors in neuronal migration and laminar organization of the cerebral cortex. Neuron 22:277-289.CrossRefPubMedGoogle Scholar
  3. Arnaud, L., Ballif, B. A., and Cooper, J. A. (2003a). Regulation of protein tyrosine kinase signaling by substrate degradation during brain development. Mol. Cell. Biol. 23:9293-9302.CrossRefPubMedGoogle Scholar
  4. Arnaud, L., Ballif, B. A., Forster, E., and Cooper, J. A. (2003b). Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Curr. Biol. 13:9-17.CrossRefPubMedGoogle Scholar
  5. Assadi, A. H., Zhang, G., Beffert, U., McNeil, R. S., Renfro, A. L., Niu, S., Quattrocchi, C. C., Antalffy, B. A., Sheldon, M., Armstrong, D. D., Wynshaw-Boris, A., Herz, J., D’Arcangelo, G., and Clark, G. D. (2003). Interaction of reelin signaling and Lis1 in brain development. Nat. Genet. 35:270-276.CrossRefPubMedGoogle Scholar
  6. Ballif, B. A., Arnaud, L., Arthur, W. T., Guris, D., Imamoto, A., and Cooper, J. A. (2004). Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr. Biol. 14:606-610.CrossRefPubMedGoogle Scholar
  7. Beffert, U., Morfini, G., Bock, H. H., Reyna, H., Brady, S. T., and Herz, J. (2002). Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3beta. J. Biol. Chem. 277:49958-49964.CrossRefPubMedGoogle Scholar
  8. Beffert, U., Weeber, E. J., Morfini, G., Ko, J., Brady, S. T., Tsai, L. H., Sweatt, J. D., and Herz, J. (2004). Reelin and cyclin-dependent kinase 5-dependent signals cooperate in regulating neuronal migration and synaptic transmission. J. Neurosci. 24:1897-1906.CrossRefPubMedGoogle Scholar
  9. Beffert, U., Weeber, E. J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J. D., Li, W. P., Adelmann, G., Frotscher, M., Hammer, R. E., and Herz, J. (2005). Modulation of synaptic plasticity and memory by reelin involves differential splicing of the lipoprotein receptor apoer2. Neuron 47:567-579.CrossRefPubMedGoogle Scholar
  10. Bock, H. H., and Herz, J. (2003). Reelin activates SRC family tyrosine kinases in neurons. Curr. Biol. 13:18-26.CrossRefPubMedGoogle Scholar
  11. Bock, H. H., Jossin, Y., Liu, P., Forster, E., May, P., Goffinet, A. M., and Herz, J. (2003). Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination. J. Biol. Chem. 278:38772-38779.CrossRefPubMedGoogle Scholar
  12. Bock, H. H., Jossin, Y., May, P., Bergner, O., and Herz, J. (2004). Apolipoprotein E receptors are required for reelin-induced proteasomal degradation of the neuronal adaptor protein Disabled-1. J. Biol. Chem. 279:33471-33479.CrossRefPubMedGoogle Scholar
  13. Brich, J., Shie, F. S., Howell, B. W., Li, R., Tus, K., Wakeland, E. K., Jin, L. W., Mumby, M., Churchill, G., Herz, J., and Cooper, J. A. (2003). Genetic modulation of tau phosphorylation in the mouse. J. Neurosci. 23:187-192.PubMedGoogle Scholar
  14. Caviness, V. S., Jr., and Rakic, P. (1978). Mechanisms of cortical development: a view from mutations in mice. Annu. Rev. Neurosci. 1:297-326.CrossRefPubMedGoogle Scholar
  15. Chen, K., Ochalski, P. G., Tran, T. S., Sahir, N., Schubert, M., Pramatarova, A., and Howell, B. W. (2004). Interaction between Dab1 and CrkII is promoted by Reelin signaling. J. Cell. Sci. 117:4527-4536.CrossRefPubMedGoogle Scholar
  16. D’Arcangelo, G., Miao, G. G., Chen, S. C., Soares, H. D., Morgan, J. I., and Curran, T. (1995). A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374:719-723.CrossRefPubMedGoogle Scholar
  17. D’Arcangelo, G., Homayouni, R., Keshvara, L., Rice, D. S., Sheldon, M., and Curran, T. (1999). Reelin is a ligand for lipoprotein receptors. Neuron 24:471-479.CrossRefPubMedGoogle Scholar
  18. Dong, E., Caruncho, H., Liu, W. S., Smalheiser, N. R., Grayson, D. R., Costa, E., and Guidotti, A. (2003). A reelin-integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes. Proc. Natl. Acad. Sci. USA 100:5479-5484.CrossRefPubMedGoogle Scholar
  19. Dulabon, L., Olson, E. C., Taglienti, M. G., Eisenhuth, S., McGrath, B., Walsh, C. A., Kreidberg, J. A., and Anton, E. S. (2000). Reelin binds alpha3beta1 integrin and inhibits neuronal migration. Neuron 27:33-44.CrossRefPubMedGoogle Scholar
  20. Fatemi, S. H. (2005). Reelin glycoprotein: structure, biology and roles in health and disease. Mol. Psychiatry 10:251-257.CrossRefPubMedGoogle Scholar
  21. Forster, E., Tielsch, A., Saum, B., Weiss, K. H., Johanssen, C., Graus-Porta, D., Muller, U., and Frotscher, M. (2002). Reelin, disabled 1, and beta 1 integrins are required for the formation of the radial glial scaffold in the hippocampus. Proc. Natl. Acad. Sci. USA 99:13178--3183.CrossRefPubMedGoogle Scholar
  22. Gonzalez-Billault, C., Del Rio, J. A., Urena, J. M., Jimenez-Mateos, E. M., Barallobre, M. J., Pascual. M., Pujadas, L., Simo, S., Torre, A. L., Gavin, R., Wandosell, F., Soriano, E., and Avila, J. (2005). A role of MAP1B in reelin-dependent neuronal migration. Cereb. Cortex 15:1134-1145.CrossRefPubMedGoogle Scholar
  23. Graus-Porta, D., Blaess, S., Senften, M., Littlewood-Evans, A., Damsky, C., Huang, Z., Orban, P., Klein, R., Schittny, J. C., and Muller, U. (2001). Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex. Neuron 31:367-379.CrossRefPubMedGoogle Scholar
  24. Harada, A., Oguchi, K., Okabe, S., Kuno, J., Terada, S., Ohshima, T., Sato-Yoshitake, R., Takei, Y., Noda, T., and Hirokawa, N. (1994). Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 369:488-491.CrossRefPubMedGoogle Scholar
  25. Herrick, T. M., and Cooper, J. A. (2002). A hypomorphic allele of dab1 reveals regional differences in reelin-Dab1 signaling during brain development. Development 129:787-796.PubMedGoogle Scholar
  26. Hiesberger, T., Trommsdorff, M., Howell, B. W., Goffinet, A., Mumby, M. C., Cooper, J. A., and Herz, J. (1999). Direct binding of reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24:481-489.CrossRefPubMedGoogle Scholar
  27. Howell, B. W., Hawkes, R., Soriano, P., and Cooper, J. A. (1997). Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389:733-737.CrossRefPubMedGoogle Scholar
  28. Howell, B. W., Herrick, T. M., and Cooper, J. A. (1999a). Reelin-induced tryosine phosphorylation of disabled 1 during neuronal positioning. Genes Dev. 13:643-648.CrossRefPubMedGoogle Scholar
  29. Howell, B. W., Lanier, L. M., Frank, R., Gertler, F. B., and Cooper, J. A. (1999b). The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. Mol. Cell. Biol. 19:5179-5188.PubMedGoogle Scholar
  30. Howell, B. W., Herrick, T. M., Hildebrand, J. D., Zhang, Y., and Cooper, J. A. (2000). Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development. Curr. Biol. 10:877-885.CrossRefPubMedGoogle Scholar
  31. Huang, Y., Magdaleno, S., Hopkins, R., Slaughter, C., Curran, T., and Keshvara, L. (2004). Tyrosine phosphorylated disabled 1 recruits Crk family adapter proteins. Biochem. Biophys. Res. Commun. 318:204-212.CrossRefPubMedGoogle Scholar
  32. Huang, Y., Shah, V., Liu, T., and Keshvara, L. (2005). Signaling through disabled 1 requires phosphoinositide binding. Biochem. Biophys. Res. Commun. 331:1460-1468.CrossRefPubMedGoogle Scholar
  33. Impagnatiello, F., Guidotti, A. R., Pesold, C., Dwivedi, Y., Caruncho, H., Pisu, M. G., Uzunov, D. P., Smalheiser, N. R., Davis, J. M., Pandey, G. N., Pappas, G. D., Tueting, P., Sharma, R. P., and Costa, E. (1998). A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc. Natl. Acad. Sci. USA 95:15718-15723.CrossRefPubMedGoogle Scholar
  34. Jossin, Y. (2004). Neuronal migration and the role of reelin during early development of the cerebral cortex. Mol. Neurobiol. 30:225-251.CrossRefPubMedGoogle Scholar
  35. Jossin, Y., Ogawa, M., Metin, C., Tissir, F., and Goffinet, A. M. (2003). Inhibition of SRC family kinases and non-classical protein kinases C induce a reeler-like malformation of cortical plate development. J. Neurosci. 23:9953-9959.PubMedGoogle Scholar
  36. Jossin, Y., Ignatova, N., Hiesberger, T., Herz, J., Lambert de Rouvroit, C., and Goffinet, A. M. (2004). The central fragment of reelin, generated by proteolytic processing in vivo, is critical to its function during cortical plate development. J. Neurosci. 24:514-521.CrossRefPubMedGoogle Scholar
  37. Keshvara, L., Benhayon, D., Magdaleno, S., and Curran, T. (2001). Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1. J. Biol. Chem. 276:16008-16014.CrossRefPubMedGoogle Scholar
  38. Keshvara, L., Magdaleno, S., Benhayon, D., and Curran, T. (2002). Cyclin-dependent kinase 5 phosphorylates disabled 1 independently of reelin signaling. J. Neurosci. 22:4869-4877.PubMedGoogle Scholar
  39. Kuo, G., Arnaud, L., Kronstad-O’Brien, P., and Cooper, J. A. (2005). Absence of Fyn and Src causes a reeler-like phenotype. J. Neurosci. 25:8578-8586.CrossRefPubMedGoogle Scholar
  40. Lambert de Rouvroit, C., de Bergeyck, V., Cortvrindt, C., Bar, I., Eeckhout, Y., and Goffinet, A. M. (1999). Reelin, the extracellular matrix protein deficient in reeler mutant mice, is processed by a metalloproteinase. Exp. Neurol. 156:214-217.CrossRefPubMedGoogle Scholar
  41. Liu, W. S., Pesold, C., Rodriguez, M. A., Carboni, G., Auta, J., Lacor, P., Larson, J., Condie, B. G., Guidotti, A., and Costa, E. (2001). Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse. Proc. Natl. Acad. Sci. US. 98:3477-3482.CrossRefGoogle Scholar
  42. Luque, J. M., Morante-Oria, J., and Fairen, A. (2003). Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development. Brain Res. Dev. Brain Res. 140:195-203.CrossRefPubMedGoogle Scholar
  43. Miyata, T., Nakajima, K., Mikoshiba, K., and Ogawa, M. (1997). Regulation of Purkinje cell alignment by reelin as revealed with CR-50 antibody. J. Neurosci. 17:3599-3609.PubMedGoogle Scholar
  44. Morimura, T., Hattori, M., Ogawa, M., and Mikoshiba, K. (2005). Disabled1 regulates the intracellular trafficking of reelin receptors. J. Biol. Chem. 280:16901-16908.CrossRefPubMedGoogle Scholar
  45. Nogi, T., Yasui, N., Hattori, M., Iwasaki, K., and Takagi, J. (2006). Structure of a signaling-competent reelin fragment revealed by X-ray crystallography and electron tomography. EMBO J. 25:3675-3683.CrossRefPubMedGoogle Scholar
  46. Ohshima, T., Ogawa, M., Veeranna, Hirasawa, M., Longenecker, G., Ishiguro, K., Pant, H. C., Brady, R. O., Kulkarni, A. B., and Mikoshiba, K. (2001). Synergistic contributions of cyclin-dependent kinase 5/p35 and reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain. Proc. Natl. Acad. Sci. USA 98:2764-2769.CrossRefPubMedGoogle Scholar
  47. Pramatarova, A., Ochalski, P. G., Chen, K., Gropman, A., Myers, S., Min, K. T., and Howell, B. W. (2003). Nck beta interacts with tyrosine-phosphorylated disabled 1 and redistributes in reelin-stimulated neurons. Mol. Cell. Biol. 23:7210-7221.CrossRefPubMedGoogle Scholar
  48. Sanada, K., Gupta, A., and Tsai, L. H. (2004). Disabled-1-regulated adhesion of migrating neurons to radial glial fiber contributes to neuronal positioning during early corticogenesis. Neuron 42:197-211.CrossRefPubMedGoogle Scholar
  49. Schiffmann, S. N., Bernier, B., and Goffinet, A. M. (1997). Reelin mRNA expression during mouse brain development. Eur. J. Neurosci. 9:1055-1071.CrossRefPubMedGoogle Scholar
  50. Schmid, R. S., Jo, R., Shelton, S., Kreidberg, J. A., and Anton, E. S. (2005). Reelin, integrin and DAB1 interactions during embryonic cerebral cortical development. Cereb. Cortex 15:1632-1636.CrossRefPubMedGoogle Scholar
  51. Senzaki, K., Ogawa, M., and Yagi, T. (1999). Proteins of the CNR family are multiple receptors for reelin. Cell 99:635-647.CrossRefPubMedGoogle Scholar
  52. Sheldon, M., Rice, D. S., D’Arcangelo, G., Yoneshima, H., Nakajima, K., Mikoshiba, K., Howell, B. W., Cooper, J. A., Goldowitz, D., and Curran, T. (1997). Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature 389:730-733.CrossRefPubMedGoogle Scholar
  53. Stolt, P. C., Jeon, H., Song, H. K., Herz, J., Eck, M. J., and Blacklow, S. C. (2003). Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes. Structure 11:569-579.CrossRefPubMedGoogle Scholar
  54. Stolt, P. C., Chen, Y., Liu, P., Bock, H. H., Blacklow, S. C., and Herz, J. (2005). Phosphoinositide binding by the disabled-1 PTB domain is necessary for membrane localization and reelin signal transduction. J. Biol. Chem. 280:9671-9677.CrossRefPubMedGoogle Scholar
  55. Strasser, V., Fasching, D., Hauser, C., Mayer, H., Bock, H. H., Hiesberger, T., Herz, J., Weeber, E. J., Sweatt, J. D., Pramatarova, A., Howell, B., Schneider, W. J., and Nimpf, J. (2004). Receptor clustering is involved in reelin signaling. Mol. Cell. Biol. 24:1378-1386.CrossRefPubMedGoogle Scholar
  56. Suetsugu, S., Tezuka, T., Morimura, T., Hattori, M., Mikoshiba, K., Yamamoto, T., and Takenawa, T. (2004). Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1. Biochem. J. 384:1-8.CrossRefPubMedGoogle Scholar
  57. Takei, Y., Teng, J., Harada, A., and Hirokawa, N. (2000). Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J. Cell. Biol. 150:989-1000.CrossRefPubMedGoogle Scholar
  58. Teng, J., Takei, Y., Harada, A., Nakata, T., Chen, J., and Hirokawa, N. (2001). Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. J. Cell Biol. 155:65-76.CrossRefPubMedGoogle Scholar
  59. Trommsdorff, M., Borg, J. P., Margolis, B., and Herz, J. (1998). Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein. J. Biol. Chem. 273:33556-33560.CrossRefPubMedGoogle Scholar
  60. Trommsdorff, M., Gotthardt, M., Hiesberger, T., Shelton, J., Stockinger, W., Nimpf, J., Hammer, R. E., Richardson, J. A., and Herz, J. (1999). Reeler/disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell 97:689-701.CrossRefPubMedGoogle Scholar
  61. Utsunomiya-Tate, N., Kubo, K., Tate, S., Kainosho, M., Katayama, E., Nakajima, K., and Mikoshiba, K. (2000). Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody. Proc. Natl. Acad. Sci. USA 97:9729-9734.CrossRefPubMedGoogle Scholar
  62. Walsh, C. A., and Goffinet, A. M. (2000). Potential mechanisms of mutations that affect neuronal migration in man and mouse. Curr. Opin. Genet. Dev. 10:270-274.CrossRefPubMedGoogle Scholar
  63. Weeber, E. J., Beffert, U., Jones, C., Christian, J. M., Forster, E., Sweatt, J. D., and Herz, J. (2002). Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J. Biol. Chem. 277:39944-39952.CrossRefPubMedGoogle Scholar
  64. Xu, M., Arnaud, L., and Cooper, J. A. (2005). Both the phosphoinositide and receptor binding activities of Dab1 are required for reelin-stimulated Dab1 tyrosine phosphorylation. Brain Res. Mol. Brain Res. 139:300-305.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Yves Jossin
    • 1
    • 2
  1. 1.Faculté de Médecine, Developmental Neurobiology UnitUniversité Catholique de LouvainBrusselsBelgium
  2. 2.Division of Basic SciencesFred Hutchinson Cancer Research CenterSeattle

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