NCBI Summary:
The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes.
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
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.