Editing Reelin (section)

=== Signaling cascades ===
Reelin activates the signaling cascade of [[NOTCH1|Notch-1]], inducing the expression of [[FABP7]] and prompting progenitor cells to assume [[radial glia]]l phenotype.<ref name="pmid18593473" /> In addition, corticogenesis ''in vivo'' is highly dependent upon reelin being processed by embryonic neurons,<ref name="pmid17442808" /> which are thought to secrete some as yet unidentified [[metalloproteinase]]s that free the central signal-competent part of the protein. Some other unknown proteolytic mechanisms may also play a role.<ref name="pmid12959647" /> It is supposed that full-sized reelin sticks to the extracellular matrix fibers on the higher levels, and the central fragments, as they are being freed up by the breaking up of reelin, are able to permeate into the lower levels.<ref name="pmid17442808" /> It is possible that as [[neuroblast]]s reach the higher levels they stop their migration either because of the heightened combined expression of all forms of reelin, or due to the peculiar mode of action of the full-sized reelin molecules and its homodimers.<ref name="Reelin_book_2008" />

The intracellular adaptor [[DAB1]] binds to the VLDLR and ApoER2 through an [[NPxY]] motif and is involved in transmission of Reelin signals through these lipoprotein receptors. It becomes phosphorylated by [[Src (gene)|Src]]<ref name="pmid9009273" /> and [[FYN|Fyn]]<ref name="pmid12526739" /> kinases and apparently stimulates the [[actin]] cytoskeleton to change its shape, affecting the proportion of integrin receptors on the cell surface, which leads to the change in [[Cell adhesion|adhesion]]. Phosphorylation of DAB1 leads to its [[ubiquitination]] and subsequent degradation, and this explains the heightened levels of DAB1 in the absence of reelin.<ref name="pmid17974915" /> Such [[negative feedback]] is thought to be important for proper cortical lamination.<ref name="pmid18006681" /> Activated by two antibodies, VLDLR and ApoER2 cause DAB1 phosphorylation but seemingly without the subsequent degradation and without rescuing the [[reeler]] phenotype, and this may indicate that a part of the signal is conducted independently of DAB1.<ref name="centralfragment" />

[[File:Reelin induces GFAP and FABP7 via Notch1.jpg|thumb|280px|Reelin stimulates the progenitor cells to differentiate into radial glia, inducing the expression of radial glial marker [[FABP7|BLBP]] by affecting the [[NOTCH1]] cascade. A fragment of an [[Commons:Image:Reelin-induced radial glial phenotype is dependent on gamma-secretase activity.jpg|illustration]] from Keilani et al., 2008.<ref name="pmid18593473" />]]

A protein having an important role in [[lissencephaly]] and accordingly called [[LIS1]] ([[PAFAH1B1]]), was shown to interact with the intracellular segment of VLDLR, thus reacting to the activation of reelin pathway.<ref name="Zhang_2007_Pafah1b" />