Role for Reelin in stabilizing cortical architecture.
Reelin controls the migration of neurons and layer formation during brain development. However, recent studies have shown that disrupting Reelin function in the adult hippocampus induces repositioning of fully differentiated neurons, suggesting a stabilizing effect of Reelin on mature neuronal circuitry. Indeed, Reelin was recently found to stabilize the actin cytoskeleton by inducing cofilin phosphorylation. When unphosphorylated, cofilin acts as an actin-depolymerizing protein that promotes the disassembly of F-actin. Here, a novel hypothesis is proposed whereby decreased Reelin expression in the mature brain causes destabilization of neurons and their processes, leading to aberrant plasticity and aberrant wiring of brain circuitry. This has implications for brain disorders, such as epilepsy and schizophrenia, in which deficiencies in Reelin expression occur.
Frotscher
Michael
M
Institut für Anatomie und Zellbiologie and Zentrum für Neurowissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstr. 17, D-79104 Freiburg, Germany. Michael.Frotscher@anat.uni-freiburg.de
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D051339:Actin Depolymerizing Factors; D000199:Actins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases