The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Dab1  -  Dab, reelin signal transducer, homolog 1...

Rattus norvegicus

Synonyms: Disabled homolog 1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on Dab1

  • Most pyramidal neurons of various cortical layers express the mouse-disabled 1 (Dab1) protein, which, after phosphorylation by a soluble tyrosine kinase, functions as an adapter protein, probably mediating a modulation of cytoskeleton protein expression [1].
  • 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 [2].
  • Induced dimerization of Dab1 in HEK293 cells leads to its phosphorylation even in the absence of Reelin receptors [3].
  • As a consequence, Dab1 becomes dimerized or oligomerized on the cytosolic side of the plasma membrane, constituting the active substrate for the kinase; this process seems to be sufficient to transmit the signal and does not appear to require any coreceptor [3].
  • Reelin binding to apolipoprotein E receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to phosphorylation of disabled 1 (Dab1), an adaptor protein which associates with the intracellular domains of both receptors [3].

Biological context of Dab1

  • Reelin signaling requires activation of Src family kinases as well as tyrosine phosphorylation of the intracellular adaptor protein Disabled-1 (Dab1) [4].
  • Disabled-1 (Dab1) is an essential adaptor protein that functions in the Reelin signaling pathway and is required for the regulation of neuronal migration during embryonic development [5].
  • Here we have investigated how phosphoinositide binding by the Dab1 PTB domain influences Reelin signal transduction [5].
  • Similarly, no rescue of the reeler-like phenotype was observed in slices from mutants lacking Disabled 1 (Dab1), an adapter protein downstream of Reelin receptors [6].

Anatomical context of Dab1


Associations of Dab1 with chemical compounds

  • Structural and biochemical studies of the Dab1 PTB domain have demonstrated that this domain binds to both the NPXY peptide motif in the lipoprotein receptor tails as well as to the head group of phosphoinositide 4,5-P2 through energetically independent mechanisms [5].
  • Furthermore, all Dab1-labeled amacrine cells showed glycine transporter-1 immunoreactivity, indicating that they are glycinergic [7].
  • Here, we report the characterization of a new mouse Dab1-interacting protein that is orthologous to rat Dab2IP, a Ras-GTPase activating protein previously shown to bind to Dab2/DOC [9].
  • Here, we show that Reelin can regulate NMDA-type glutamate receptor activity through a mechanism that requires SFKs and Dab1 [10].

Physical interactions of Dab1

  • Dab1 interacts with NPXY motifs in the cytoplasmic tails of the lipoprotein receptors ApoER2 and very low density lipoprotein receptor through an amino-terminal phosphotyrosine binding (PTB) domain [5].

Other interactions of Dab1


Analytical, diagnostic and therapeutic context of Dab1

  • We investigated Dab1-labeled cells in human, rat, rabbit, and cat retinas in detail by immunocytochemistry with antisera against Dab1 [7].
  • These findings show that Reelin from other brain regions can substitute for the loss of hippocampal Reelin and that rescue of the reeler phenotype observed in our coculture studies is mediated via lipoprotein receptors for Reelin and Dab1 [6].
  • The interaction of Dab1 and Dab2IP was confirmed in biochemical assays and by co-immunoprecipitation from brain lysates [9].


  1. Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex. Rodriguez, M.A., Pesold, C., Liu, W.S., Kriho, V., Guidotti, A., Pappas, G.D., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. 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]
  3. Receptor clustering is involved in Reelin signaling. 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., Nimpf, J. Mol. Cell. Biol. (2004) [Pubmed]
  4. Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination. Bock, H.H., Jossin, Y., Liu, P., Förster, E., May, P., Goffinet, A.M., Herz, J. J. Biol. Chem. (2003) [Pubmed]
  5. Phosphoinositide binding by the disabled-1 PTB domain is necessary for membrane localization and Reelin signal transduction. Stolt, P.C., Chen, Y., Liu, P., Bock, H.H., Blacklow, S.C., Herz, J. J. Biol. Chem. (2005) [Pubmed]
  6. Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for Reelin and Disabled 1. Zhao, S., Chai, X., Bock, H.H., Brunne, B., Förster, E., Frotscher, M. J. Comp. Neurol. (2006) [Pubmed]
  7. AII amacrine cells in the mammalian retina show disabled-1 immunoreactivity. Lee, E.J., Kim, H.J., Lim, E.J., Kim, I.B., Kang, W.S., Oh, S.J., Rickman, D.W., Chung, J.W., Chun, M.H. J. Comp. Neurol. (2004) [Pubmed]
  8. Juxtaposition of CNR protocadherins and reelin expression in the developing spinal cord. Carroll, P., Gayet, O., Feuillet, C., Kallenbach, S., de Bovis, B., Dudley, K., Alonso, S. Mol. Cell. Neurosci. (2001) [Pubmed]
  9. Interaction of Disabled-1 and the GTPase activating protein Dab2IP in mouse brain. Homayouni, R., Magdaleno, S., Keshvara, L., Rice, D.S., Curran, T. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  10. Reelin modulates NMDA receptor activity in cortical neurons. Chen, Y., Beffert, U., Ertunc, M., Tang, T.S., Kavalali, E.T., Bezprozvanny, I., Herz, J. J. Neurosci. (2005) [Pubmed]
WikiGenes - Universities