Editing Reelin (section)

=== Receptors ===
Reelin's control of cell-cell interactions is thought to be mediated by binding of reelin to the two members of [[low density lipoprotein receptor gene family]]: [[VLDL receptor|VLDLR]] and the [[low density lipoprotein receptor-related protein 8|ApoER2]].<ref name="pmid10571240" /><ref name="pmid10571241" /><ref name="pmid12899622" /><ref name="pmid12670700" /> The two main reelin receptors seem to have slightly different roles: VLDLR conducts the stop signal, while ApoER2 is essential for the migration of late-born neocortical neurons.<ref name="pmid17913789" /> It also has been shown that the N-terminal region of reelin, a site distinct from the region of reelin shown to associate with VLDLR/ApoER2 binds to the alpha-3-beta-1 [[integrin]] receptor.<ref name="integrin" /> The proposal that the proto[[cadherin]] CNR1 behaves as a Reelin receptor<ref name="cadherin" /> has been disproven.<ref name="centralfragment" />

As members of lipoprotein receptor superfamily, both VLDLR and ApoER2 have in their structure an internalization domain called [[NPxY]] [[Structural motif|motif]]. After binding to the receptors reelin is internalized by [[endocytosis]], and the N-terminal fragment of the protein is re-secreted.<ref name="pmid19303411" /> This fragment may serve postnatally to prevent apical dendrites of cortical layer II/III pyramidal neurons from overgrowth, acting via a pathway independent of canonical reelin receptors.<ref name="pmid19366679" />

Reelin receptors are present on both [[neuron]]s and [[glial cell]]s. Furthermore, [[radial glia]] express the same amount of [[Low density lipoprotein receptor-related protein 8|ApoER2]] but being ten times less rich in [[VLDL receptor|VLDLR]].<ref name="pmid12925587" /> [[CD29|beta-1 integrin receptors]] on glial cells play more important role in neuronal layering than the same receptors on the migrating neuroblasts.<ref name="pmid18077697" />

Reelin-dependent strengthening of [[long-term potentiation]] is caused by [[ApoER2]] interaction with [[NMDA receptor]]. This interaction happens when ApoER2 has a region coded by exon 19. ApoER2 gene is alternatively spliced, with the exon 19-containing variant more actively produced during periods of activity.<ref name="Reelin_ApoER2_Exon19_2005_Beffert" /> According to one study, the hippocampal reelin expression rapidly goes up when there is need to store a memory, as [[demethylase]]s open up the RELN gene.<ref name="pmid17359920" /> The activation of dendrite growth by reelin is apparently conducted through [[Src (gene)|Src]] family [[kinase]]s and is dependent upon the expression of [[CRK (gene)|Crk]] family proteins,<ref name="pmid18477607" /> consistent with the interaction of Crk and CrkL with tyrosine-phosphorylated Dab1.<ref name="pmid15062102" /> Moreover, a [[Cre-Lox recombination|Cre-loxP recombination]] mouse model that lacks [[CRK (gene)|Crk]] and [[CRKL|CrkL]] in most neurons<ref name="pmid19074029" /> was reported to have the [[reeler]] phenotype, indicating that Crk/CrkL lie between [[DAB1]] and [[AKT1|Akt]] in the reelin signaling chain.