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Reelin is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation.〔〔 It also stimulates dendrite〔 and dendritic spine〔 development and regulates the continuing migration of neuroblasts generated in adult neurogenesis sites like subventricular and subgranular zones. It is found not only in the brain, but also in the spinal cord, blood, and other body organs and tissues. Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psychotic bipolar disorder, but the cause of this observation remains uncertain as studies show that psychotropic medication itself affects reelin expression. Moreover, epigenetic hypotheses aimed at explaining the changed levels of reelin expression〔 are controversial.〔〔 Total lack of reelin causes a form of lissencephaly. Reelin may also play a role in Alzheimer's disease, temporal lobe epilepsy and autism. Reelin's name comes from the abnormal reeling gait of ''reeler'' mice,〔 which were later found to have a deficiency of this brain protein and were homozygous for mutation of the RELN gene. The primary phenotype associated with loss of reelin function is a failure of neuronal positioning throughout the developing central nervous system (CNS). The mice heterozygous for the reelin gene, while having little neuroanatomical defects, display the endophenotypic traits linked to psychotic disorders.〔 == Discovery == Mutant mice have provided insight into the underlying molecular mechanisms of the development of the central nervous system. Useful spontaneous mutations were first identified by scientists who were interested in motor behavior, and it proved relatively easy to screen littermates for mice that showed difficulties moving around the cage. A number of such mice were found and given descriptive names such as reeler, weaver, lurcher, nervous, and staggerer. The "reeler" mouse was described for the first time in 1951 by D.S.Falconer in Edinburgh University as a spontaneous variant arising in a colony of mice maintained by geneticist Charlotte Auerbach.〔 Histopathological studies in the 1960s revealed that the cerebellum of reeler mice is dramatically decreased in size while the normal laminar organization found in several brain regions is disrupted.〔 The 1970s brought the discovery of cellular layers inversion in the mice neocortex,〔 which attracted more attention to the reeler mutation. In 1994, a new allele of reeler was obtained by means of insertional mutagenesis.〔 This provided the first molecular marker of the locus, permitting the RELN gene to be mapped to chromosome 7q22 and subsequently cloned and identified.〔 Japanese scientists at Kochi Medical School successfully raised antibodies against normal brain extracts in reeler mice, later these antibodies were found to be specific monoclonal antibodies for reelin, and were termed CR-50 (Cajal-Retzius marker 50).〔 They noted that CR-50 reacted specifically with Cajal-Retzius neurons, whose functional role was unknown until then. The Reelin receptors, apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR), were discovered by Trommsdorff, Herz and colleagues, who initially found that the cytosolic adaptor protein Dab1 interacts with the cytoplasmic domain of LDL receptor family members.〔 They then went on to show that the double knockout mice for ApoER2 and VLDLR, which both interact with Dab1, had cortical layering defects similar to those in reeler.〔 The downstream pathway of reelin was further clarified with the help of other mutant mice, including yotari and scrambler. These mutants have phenotypes similar to that of reeler mice, but without mutation in reelin. It was then demonstrated that the mouse ''disabled homologue 1'' (Dab1) gene is responsible for the phenotypes of these mutant mice, as Dab1 protein was absent (yotari) or only barely detectable (scrambler) in these mutants.〔 Targeted disruption of Dab1 also caused a phenotype similar to that of reeler. Pinpointing the DAB1 as a pivotal regulator of the reelin signaling cascade started the tedious process of deciphering its complex interactions. There followed a series of speculative reports linking reelin's genetic variation and interactions to schizophrenia, Alzheimer's disease, autism and other highly complex dysfunctions. These and other discoveries, coupled with the perspective of unraveling the evolutionary changes that allowed for the creation of human brain, highly intensified the research. As of 2008, some 13 years after the gene coding the protein was discovered, hundreds of scientific articles address the multiple aspects of its structure and functioning.〔〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Reelin」の詳細全文を読む スポンサード リンク
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