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Gene Review

Reln  -  reelin

Rattus norvegicus

Synonyms: Reelen, Reelin, Rl, reeler
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Disease relevance of Reln

  • With the concept that reelin might also be important for axonal growth in the injured nervous system we investigated whether reelin is re-expressed in areas of collateral sprouting after brain injury [1].
  • No significant differences in NCAM expression were seen in hippocampus, nor did reelin expression differ in cerebral cortex between control and IUGR groups [2].

High impact information on Reln

  • Reelin (Reln) is a glycoprotein that in postnatal and adult mammalian brain is believed to be secreted from telencephalic GABAergic interneurons and cerebellar glutamatergic granule neurons into the extracellular matrix [3].
  • Although, CGNs express and secrete Reln (measured by quantitative immunoblotting), none of the above-mentioned conditions that control regulated exocytosis alters the stores or the rate of Reln release [3].
  • Because, in subcellular fractionation studies, we have shown that Reln is not contained in synaptic vesicles, these data suggest that Reln secretion from CGNs does not require Ca(2+)-dependent exocytosis, but probably is related to a Reln pool stored in Golgi secretory vesicles mediating a constitutive secretory pathway [3].
  • In contrast, application of either: (i) a Reln antisense oligonucleotide (5'-GCAATGTGCAGGGAAATG-3') (10 microM) that reduces Reln biosynthesis or (ii) brefeldin A (5 x 10(-5) M), an inhibitor of the traffic of proteins between the endoplasmic reticulum and the Golgi network, sharply curtail the rate of Reln secretion [3].
  • Dab1, the target adapter protein that presumably mediates transcription regulation via the extrasynaptic actions of Reln, is expressed predominantly in pyramidal neurons, but it can also be detected in a small population of GABAergic neurons that are neither horizontal nor bitufted neurons [4].

Biological context of Reln

  • Although Reln is secreted by GABAergic neurons, its target are not the GABA receptors, but rather may be extrasynaptically located in perineuronal nets and concerned with the modulation of neuronal plasticity [4].
  • These results indicate a dual function of reelin in the dentate gyrus, as a differentiation factor for radial glial cells and as a positional cue for radial fiber orientation and granule cell migration [5].
  • From the cDNA sequences, we found a 64-base heterologous sequence in SRK reelin, which contains a termination codon in the reading frame [6].
  • Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression [4].
  • They express the neurotransmitter GABA but seem to lack the calcium binding protein calretinin; some migrating cells found in the marginal zone express reelin [7].

Anatomical context of Reln

  • However, only 50-60% of GABAergic interneurons express Reln [4].
  • The murine reeler mutants arise from several mutations in the specific gene called reelin, which result in defects of Reelin expression or secretion in the cerebral cortex and other regions of CNS [6].
  • Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord [8].
  • Northern analysis of reelin mRNA from normal rats showed that rat reelin was expressed as a approximately 12-kb transcript in both the cerebrum and the cerebellum, whereas reelin expression was markedly reduced in the SRK brains [6].
  • In situ hybridization analysis showed that reelin mRNA in the SRK brains was expressed in Cajal-Retzius cells in the marginal zone of the cerebral cortex and outer granular cells in the cerebellar cortex in similar manners to normal controls, but its expression was considerably reduced [6].

Associations of Reln with chemical compounds


Physical interactions of Reln

  • The nature and the origin of the cell populations that colonize the preplate/marginal zone was studied by means of immunohistochemistry using cell markers for gamma-amino butyric acid (GABA), reelin and the calcium binding proteins calretinin and calbindin [10].

Regulatory relationships of Reln


Other interactions of Reln

  • Basket and chandelier cells are often immunopositive to parvalbumin, but never to Reln [4].
  • Reelin (Reln) is a protein with some structural analogies with other extracellular matrix proteins that functions in the regulation of neuronal migration during the development of cortical laminated structures [4].
  • The predominant cell type in the marginal zone is the Cajal-Retzius cell, which expresses reelin and calretinin, and is probably generated in the cortical neuroepithelium [10].
  • Cells double labeled for reelin and the GABA synthesizing enzyme glutamic acid decarboxylase represented about 4% of the total neuron population in culture and their density remained constant with age [11].

Analytical, diagnostic and therapeutic context of Reln


  1. Entorhinal cortex lesion does not alter reelin messenger RNA expression in the dentate gyrus of young and adult rats. Haas, C.A., Deller, T., Krsnik, Z., Tielsch, A., Woods, A., Frotscher, M. Neuroscience (2000) [Pubmed]
  2. Underexpression of neural cell adhesion molecule and neurotrophic factors in rat brain following thromboxane A(2)-induced intrauterine growth retardation. Fukami, E., Nakayama, A., Sasaki, J., Mimura, S., Mori, N., Watanabe, K. Early Hum. Dev. (2000) [Pubmed]
  3. Reelin secretion from glutamatergic neurons in culture is independent from neurotransmitter regulation. Lacor, P.N., Grayson, D.R., Auta, J., Sugaya, I., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression. Pesold, C., Liu, W.S., Guidotti, A., Costa, E., Caruncho, H.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Reelin is a positional signal for the lamination of dentate granule cells. Zhao, S., Chai, X., Förster, E., Frotscher, M. Development (2004) [Pubmed]
  6. Missplicing resulting from a short deletion in the reelin gene causes reeler-like neuronal disorders in the mutant shaking rat Kawasaki. Kikkawa, S., Yamamoto, T., Misaki, K., Ikeda, Y., Okado, H., Ogawa, M., Woodhams, P.L., Terashima, T. J. Comp. Neurol. (2003) [Pubmed]
  7. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. Lavdas, A.A., Grigoriou, M., Pachnis, V., Parnavelas, J.G. J. Neurosci. (1999) [Pubmed]
  8. Developmental distribution of reelin-positive cells and their secreted product in the rodent spinal cord. Kubasak, M.D., Brooks, R., Chen, S., Villeda, S.A., Phelps, P.E. J. Comp. Neurol. (2004) [Pubmed]
  9. Thyroid hormone regulates reelin and dab1 expression during brain development. Alvarez-Dolado, M., Ruiz, M., Del Río, J.A., Alcántara, S., Burgaya, F., Sheldon, M., Nakajima, K., Bernal, J., Howell, B.W., Curran, T., Soriano, E., Muñoz, A. J. Neurosci. (1999) [Pubmed]
  10. Origin of the cortical layer I in rodents. Jiménez, D., Rivera, R., López-Mascaraque, L., De Carlos, J.A. Dev. Neurosci. (2003) [Pubmed]
  11. Reelin immunoreactivity in dissociated cultures of the postnatal hippocampus. Scotti, A.L., Herrmann, G. Brain Res. (2002) [Pubmed]
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