Emerging topics in Reelin function

Abstract

Reelin signalling in the early developing cortex regulates radial migration of cortical neurons. Later in development, Reelin promotes maturation of dendrites and dendritic spines. Finally, in the mature brain, it is involved in modulating synaptic function. In recent years, efforts to identify downstream signalling events induced by binding of Reelin to lipoprotein receptors led to the characterization of novel components of the Reelin signalling cascade. In the present review, we first address distinct functions of the Reelin receptors Apoer2 and Vldlr in cortical layer formation, followed by a discussion on the recently identified downstream effector molecule n-cofilin, involved in regulating actin cytoskeletal dynamics required for coordinated neuronal migration. Next, we discuss possible functions of the recently identified Reelin-Notch signalling crosstalk, and new aspects of Reelin´s role in the formation of the dentate radial glial scaffold. Finally, progress in characterizing the function of Reelin in modulating synaptic function in the adult brain is summarized. The present review has been inspired by a session entitled "Functions of Reelin in the developing and adult hippocampus", held at the Spring

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

“…Other potential mechanisms by which ApoE receptors may promote neuronal survival (Beffert et al 2006b) during aging involve signaling pathways that control microtubule and actin dynamics Assadi et al 2003;Brich et al 2003;Ohkubo et al 2003;Chai et al 2009;Forster et al 2010;Rust et al 2010), dendritogenesis (Niu et al 2004), spine formation (Niu et al 2008), glutamate receptor function and synaptic plasticity (Zhuo et al 2000;Weeber et al 2002;Beffert et al 2005;Chen et al 2005;D'Arcangelo 2005;Sinagra et al 2005;Groc et al 2007;Durakoglugil et al 2009;Korwek et al 2009;Chen et al 2010), as well as learning and memory (reviewed in Herz and Beffert 2000;Herz and Chen 2006;Bu 2009;Herz 2009). In this section we will mainly focus on the role of the ApoE receptors Apoer2 and Vldlr and their ligand Reelin in these processes.…”

Rare autosomal copy number variations in early-onset familial Alzheimer’s disease

“…71 VLDLR has been reported to be involved in multiple AD-related pathways, including acting as a receptor for APOE as well as roles in Tau phosphorylation and synaptic functioning via interaction with RELN. 72,73 Numerous pathogenic mutations in VLDLR have also been reported to cause cerebral ataxia and mental retardation (OMIM: 224050).…”

Clusterin Is a Ligand for Apolipoprotein E Receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR) and Signals via the Reelin-signaling Pathway

“…Phosphorylated Dab1 activates phosphatidylinositide 3-kinase (PI3K) and subsequently PKB/Akt, which in turn inhibits the activity of GSK3␤ (8). Other downstream events are still poorly understood (9), but involve cullin-5 to regulate the degradation of Dab1 (10) and activation of cofilin which links the Reelin-signaling cascade to the dynamics of actin filaments (11). In addition, Reelin signals via the small GTPase Rap1 to effect the localization of N-cadherin which polarizes migrating neuroblasts toward the radial morphology zone of the cerebral cortex (12).…”