Reelin modulates cytoskeletal organization by regulating Rho GTPases

Abstract

The correct positioning of postmitotic neurons in the developing neocortex and other laminated brain structures requires the activation of a Reelin-lipoprotein receptor-Dab1 signaling cascade. The large glycoprotein Reelin is secreted by Cajal-Retzius pioneer neurons and bound by the apolipoprotein E receptor family members Apoer2 and Vldl receptor on responsive neurons and radial glia. This leads to the tyrosine phosphorylation of the cytoplasmic protein Disabled-1 (Dab1) by non-receptor tyrosine kinases of the Src family. Various signaling pathways downstream of Dab1 connect Reelin to the actin and microtubule cytoskeleton. Despite this knowledge, a comprehensive view linking the different cell-biological and biochemical actions of Reelin to its diverse physiological roles not only during neurodevelopment but also in the maintenance and functioning of the adult brain is still lacking. In this review, we discuss our finding that Reelin activates Rho GTPases in neurons in the light of other recent studies, which demonstrate a role of Reelin in Golgi organization, and suggest additional roles of Cdc42 activation by Reelin in radial glial cells of the developing cortex. © 2011 Landes Bioscience.