Canonical and Non-canonical Reelin Signaling

• Published in: Frontiers in cellular neuroscience Vol. 10; p. 166
• Main Authors: Bock, Hans H, May, Petra
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 30.06.2016; Frontiers Media S.A
• Subjects: Adaptor proteins; Apolipoprotein E; Cytoskeleton; Disabled-1 protein; Genotype & phenotype; Kinases; Lipoprotein receptors; Low density lipoprotein receptors; Molecular modelling; Neurons; Neuroscience; Phosphorylation; Protein kinase; Protein kinase C; Proteins; Receptor density; Reelin protein; Rodents; Roles; Signal transduction; Synaptic plasticity; Tyrosine; neuronal development; Alzheimer disease; amyloid precursor protein; coreceptor; synaptic plasticity; integrin; Eph receptor; protein kinase
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2016.00166

Reelin is a large secreted glycoprotein that is essential for correct neuronal positioning during neurodevelopment and is important for synaptic plasticity in the mature brain. Moreover, Reelin is expressed in many extraneuronal tissues; yet the roles of peripheral Reelin are largely unknown. In the brain, many of Reelin's functions are mediated by a molecular signaling cascade that involves two lipoprotein receptors, apolipoprotein E receptor-2 (Apoer2) and very low density-lipoprotein receptor (Vldlr), the neuronal phosphoprotein Disabled-1 (Dab1), and members of the Src family of protein tyrosine kinases as crucial elements. This core signaling pathway in turn modulates the activity of adaptor proteins and downstream protein kinase cascades, many of which target the neuronal cytoskeleton. However, additional Reelin-binding receptors have been postulated or described, either as coreceptors that are essential for the activation of the "canonical" Reelin signaling cascade involving Apoer2/Vldlr and Dab1, or as receptors that activate alternative or additional signaling pathways. Here we will give an overview of canonical and alternative Reelin signaling pathways, molecular mechanisms involved, and their potential physiological roles in the context of different biological settings.