The extracellular matrix protein Reelin, secreted by Cajal-Retzius cells in the marginal zone of the cortex, controls the radial migration of cortical neurons. Reelin signaling involves the lipoprotein receptors apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR), the adapter protein Disabled1 (Dab1), and phosphatidylinositol-3-kinase (PI3K). Eventually, Reeli...

Migration of neurons during cortical development is often assumed to rely on purely post-proliferative reelin signaling. However, Notch signaling, long known to regulate neural precursor formation and maintenance, is required for the effects of reelin on neuronal migration. Here, we show that reelin gain-of-function causes a higher expression of Notch target genes in radial glia and accelerates...

Adult hippocampal neurogenesis is thought to be essential for learning and memory, and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an e...

The processing of amyloid precursor protein (APP) to Abeta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and Abeta production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functi...

Reelin is a signaling protein increasingly associated with the pathogenesis of Alzheimer's disease that relevantly modulates tau phosphorylation. We have previously demonstrated that β-amyloid peptide (Aβ) alters reelin expression. We have now attempted to determine whether abnormal reelin triggered by Aβ will result in signaling malfunction, contributing to the pathogenic process. Here, we sho...

Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer's diseases (AD) tissues including cerebral...

Reelin is an extracellular protein that controls many aspects of pre- and postnatal brain development and function. The molecular mechanisms that mediate postnatal activities of Reelin are not well understood. Here, we first set out to express and purify the full length Reelin protein and a biologically active central fragment. Second, we investigated in detail the signal transduction mechanism...

Cerebellar Purkinje cells are generated in the ventricular zone, migrate outward, and finally form a monolayer in the cortex. In reeler mice, however, most Purkinje cells cluster abnormally in subcortical areas. Reelin, the candidate reeler gene product recognized by the CR-50 monoclonal antibody, is concentrated in a cortical zone along which Purkinje cells are aligned linearly, implying that ...

In addition to the fundamental role of the extracellular glycoprotein Reelin in neuronal development and adult synaptic plasticity, alterations in Reelin-mediated signaling have been suggested to contribute to neuronal dysfunction associated with Alzheimer’s disease (AD). In vitro data revealed a biochemical link between Reelin-mediated signaling, Tau phosphorylation, and amyloid precursor prot...

The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depressio...