Reelin is an extracellular glycoprotein involved in neuronal development, specifically in the brain cortex. It contains 8 tandemly repeated units, each of which is composed of two highly similar subrepeats and a central EGF domain. Some family members appear to have an additional subrepeat at the N-terminus as characterized in this model. Consecutive reelin repeat units are packed together to form an overall rod-like molecular structure. Reelin repeats 5 and 6 are reported to interact with neuronal receptors, the apolipoprotein E receptor 2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR), triggering a signaling cascade upon binding and subsequent tyrosine phosphorylation of the cytoplasmic disabled-1 (Dab1). Genetic deficiency of reelin, or ApoER2 and VLDLR, or Dab1, all exhibit the same phenotypes, including ataxia, cortical layer inversion and abnormal positioning patterns.
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