Editors' ChoiceLipoprotein receptors

Lipoprotein receptors: Binding to Reelin in the Brain

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Science's STKE  26 Oct 1999:
Vol. 1999, Issue 5, pp. tw5
DOI: 10.1126/stke.1999.5.tw5

The extracellular protein Reelin directs proper formation of neural layers in the brain during development. Two groups have now identified the very low-density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor (ApoER2) as receptors for Reelin, which explains why Reelin-deficient mice and mice that lack both lipoprotein receptors exhibit a similar neuronal phenotype. Reelin bound to both receptors with high affinity, and upon binding, was internalized into endosomes. Blocking ligand-receptor interaction with specific antibodies or competing proteins prevented Reelin-induced phosphorylation of Disabled (Dab1), an intracellular adaptor protein in Reelin target cells. The data presented by both groups indicates that the two lipoprotein receptors are components of the Reelin signal transduction cascade that regulates neuronal migration in the brain. However, it has yet to be determined how phosphorylation of Dab1 occurs because neither receptor has intrinsic kinase activity.

D'Arcangelo, G., Homayouni, R., Keshvara, L., Rice, D.S., Sheldon, M., and Curran, T. (19990 Reelin is a ligand for lipoprotein receptors. Neuron 24: 471-479. [Online Journal]

Hiesberger, T., Trommsdorff, M., Howell, B.W., Goffinet, A., Mumby, M.C., Cooper, J.A., and Herz, J. (19990 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. [Online Journal]

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