Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1). Phosphorylated Dab1 (pDab1) is a hub in the signaling cascade, from which several other downstream pathways diverge reflecting the different roles of reelin. Many of these pathways affect the dynamics of the actin and microtubular cytoskeleton, as well as membrane trafficking through the regulation of the activity of small GTPases, including the Rho and Rap families and molecules involved in cell polarity. The complexity of reelin functions is reflected by the fact that, even now, the precise mode of action of this signaling cascade in vivo at the cellular and molecular levels remains unclear. This review addresses and discusses in detail the participation of reelin in the processes underlying neurogenesis, neuronal migration in the cerebral cortex and the hippocampus; and the polarization, differentiation and maturation processes that neurons experiment in order to be functional in the adult brain. In vivo and in vitro evidence is presented in order to facilitate a better understanding of this fascinating system.
-
Cover Image
Cover Image
Multiple protein sequence alignment of the E3 ubiquitin ligase RNF52 from the yeasts (Schizosaccharomyces pombe and Saccharomyces cerevisiae), dimorphic fungus (Candida albicans), thale cress (Arabidopsis thaliana), roundworm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), African clawed frog (Xenopus laevis), chicken (Gallus gallus), American alligator (Alligator mississippiensis), human, and mouse (Mus musclus). In this issue of the Biochemical Journal, Shoji et al. report on the role of BRAP, the human form of RNF52, in the oligomeric ubiquitylation process; for details see pages 3207–3226.
The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation
Jessica Santana, María-Paz Marzolo; The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation. Biochem J 15 September 2017; 474 (18): 3137–3165. doi: https://doi.org/10.1042/BCJ20160628
Download citation file:
Sign in
Sign in to your personal account
Captcha Validation Error. Please try again.