NCBI Summary:
This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
General function
Ligand, Cell adhesion molecule
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Cellular localization
Extracellular Matrix, Secreted
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Ovarian function
Antral follicle growth, Steroid metabolism
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Reelin and aromatase cooperate in ovarian follicle development. Meseke M et al. (2018) Reelin plays an important role in cerebral cortex development and synaptogenesis. In the hippocampus, the neurosteroid estrogen affects reelin expression. In this study we tested a potential crosstalk between estradiol and reelin, thus the possibility of a reelin-induced activation of the estradiol synthesizing enzyme aromatase. As a model system, we used ovaries, which express reelin and are a major source of estradiol. We found that in wild-type mice, reelin and aromatase are expressed in granulosa cells of growing follicles. The expression of reelin varies with the estrus cycle and is highest shortly before ovulation, when estradiol serum levels are at their maximum. In ovaries of reelin-deficient reeler mice, aromatase mRNA and protein are significantly reduced, as evidenced by real-time PCR, western blot analysis, and quantitative immunohistochemistry in granulosa cells of preovulatory follicles. In line with reduced estradiol synthesis, ovarian estrus cycle length is prolonged in reeler mice. Most importantly, treating cultured granulosa cells with recombinant reelin results in significant upregulation of aromatase mRNA and protein and increased secretion of estradiol into the supernatant. Our data provide evidence of a local increase of aromatase expression by reelin. Regarding reproduction, this crosstalk may contribute to follicular stability and counteract luteinization in ovaries.//////////////////
Signalling by the extracellular matrix protein Reelin promotes granulosa cell proliferation in the chicken follicle. Eresheim C 2014 et al.
Chicken oocytes develop in follicles and reach an enormous size due to massive uptake of yolk precursors such as very low density lipoprotein and vitellogenin. Oocyte growth is supported by theca cells and granulosa cells which establish dynamic and highly organized cell layers surrounding the oocyte. Signalling processes orchestrating the development of these layered structures are largely unknown. Here we demonstrate that the Reelin pathway which determines the development of layered neuronal structures in the brain is also active in chicken follicles. Reelin, which is expressed in theca cells triggers a signal in granulosa cells via apolipoprotein E receptor 2 and very low density lipoprotein receptor resulting in the phosphorylation of disabled-1 and consecutive activation of the phosphatidylinositol-3-kinase/Akt pathway. This signalling pathway supports proliferation of differentiated granulosa cells to keep up with the demand of cells to cover the rapidly increasing surface of the giant germ cell.
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Expression regulated by
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Ovarian localization
Granulosa, Theca
Comment
This gene was found in a mouse DNA array analysis of transcripts expressed in mouse preovulatory follicles.
////// Low-Density Lipoprotein Receptor-Related 8 (LRP8) Is Upregulated in Granulosa Cells of Bovine Dominant Follicle: Molecular Characterization and Spatio-Temporal Expression Studies. Fayad T et al. The low-density lipoprotein (LDL) receptor-related protein 8 (LRP8) is a member of the LDL receptor family that acts in endocytosis and in signal transduction. We cloned the fulllength bovine LRP8 cDNA in granulosa cells (GC) of dominant follicle (DF) as well as several LRP8 mRNA splicing variants, including a variant containing a proline-rich cytoplasmic insert (A(759)-K(817)) involved in intracellular signaling. Expression of the A(759)-K(817) variant was analyzed in GC of follicles at different developmental stages: small follicle (SF; 2-4 mm), DF at day 5 (D5) of the estrous cycle, ovulatory follicles (OF) 24 h after hCG injection, and corpus luteum (CL) at D5. RT-PCR results show that expression is predominant in GC of DF compared to other follicles and CL (P < 0.0001) whereas other related receptors such as LDLR and VLDLR expression does not differ. Temporal analyses of follicular walls from OF following hCG treatment reveal a decrease of LRP8 mRNA expression starting 12 h post-hCG treatment (P < 0.0001). LRP8 protein is exclusively localized in GC with highest levels in DF when compared to SF (P < 0.05). We show that RELN mRNA, encoding an LRP8 ligand, is highly expressed in theca of DF when compared to OF (P < 0.004), whereas MAPK8IP1 mRNA, encoding an LRP8 intracellular interacting partner is expressed in GC of DF. These results demonstrate the differential expression of LRP8, RELN and MAPK8IP1 mRNAs during final follicular growth and ovulation, and suggest that a RELN/LRP8/MAPK8IP1 paracrine interaction may regulate follicular growth.