Cloning of a complementary deoxyribonucleic acid encoding the murine homolog of the very low density lipoprotein/apolipoprotein-E receptor: expression pattern and assignment of the gene to mouse chromosome 19.

Abstract

We report the cloning of a complementary DNA for the mouse homolog of the very low density lipoprotein (VLDL)/apolipoprotein-E receptor (VLDLR), the deduced amino acid sequence of the protein, and the mapping of the gene encoding the receptor to mouse chromosome 19. Northern hybridization revealed that the VLDLR messenger RNA (mRNA) is most abundant in skeletal muscle, heart, kidney, and brain. It was also detected in lung and in low levels in liver, but it was not found in spleen or testes. Levels of VLDLR mRNA in mouse placenta increased from days 8-18 of gestation. The VLDLR mRNA was induced in 3T3-L1 cells undergoing differentiation into adipocytes. The increase in VLDLR mRNA paralleled the rise in lipoprotein lipase and hormone-sensitive lipase mRNAs. However, VLDLR and low density lipoprotein receptor-related protein were increased in the presence of retinoic acid, whereas the induction of lipoprotein lipase and hormone-sensitive lipase mRNAs was inhibited. Our observations demonstrate regulated expression of the VLDLR gene in placenta and adipocytes, where the receptor protein may play roles in the uptake of triglyceride-rich particles for storage of lipid (adipocytes) or for lipid transport to the fetus (placenta). The availability of a murine complementary DNA probe and the knowledge of the map position of the VLDLR gene in the mouse genome will facilitate studies on the function and regulation of this protein.

Regulation of the Ligand Binding Activity of the Human Very Low Density Lipoprotein Receptor by Protein Kinase C-dependent Phosphorylation

“…More recently, however, Bu et al (81) demonstrate that the LDL receptor-related protein/␣ 2 -macroglobulin receptor is phosphorylated in neuronal cells in response to nerve growth factor, leading to enhanced expression and endocytic activity. Our studies suggest that the cytoplasmic domain of the VLDL-R plays an important role in regulating receptor function, a hypothesis consistent with the complete sequence conservation of this domain in the murine (38,82), rabbit (6), and human (35-37) receptors. Trommsdorf et al (83) also demonstrate a critical role for the cytoplasmic domains of the VLDL-R and apoE receptor 2 in binding of the cytoplasmic adaptor protein mammalian Disabled (mDab1), an interaction critical for appropriate migration and layering of neurons during development of the cerebellum and cerebral cortex.…”

PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain

“…Because VLDLR and ApoER2 are highly expressed in the central nervous system (CNS) and have been previously implicated in Alzheimer's disease (AD) pathology (22)(23)(24)(25)(26), we sought to investigate their potential modulation by PCSK9 in vivo. It has also been recently shown that overexpression of PCSK9 in cells decreased cellular levels of the ␤ -site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), a membrane protease responsible for the production of toxic ␤ -amyloid peptides (A ␤ ) that accumulate in neuritic plaques of AD brains ( 27,28 ).…”

Chicken Oocytes and Somatic Cells Express Different Splice Variants of a Multifunctional Receptor

“…In this context, the expression of LR8 in mammals is of interest. In contrast to the major site of expression in oviparous species, the ovary, mammalian LR8s are found in tissues with active metabolism of fatty acids, such as skeletal muscle, heart, adipose tissue, and brain (Takahashi et al, 1992;Gåfvels et al, 1993Gåfvels et al, , 1994Oka et al, 1994b;Webb et al, 1994;Jokinen et al, 1994). The chicken oocyte, on the other hand, avidly takes up yolk proteins including VLDL, not for immediate catabolism but rather for storage and later use as energy supply for the developing embryo.…”