The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor

Abstract

Apolipoprotein E receptor 2 (ApoER2) and VLDL receptor belong to the low density lipoprotein receptor family and bind apolipoprotein E. These receptors interact with the clathrin machinery to mediate endocytosis of macromolecules but also interact with other adapter proteins to perform as signal transduction receptors. The best characterized signaling pathway in which ApoER2 and VLDL receptor (VLDLR) are involved is the Reelin pathway. This pathway plays a pivotal role in the development of laminated structures of the brain and in synaptic plasticity of the adult brain. Since Reelin and apolipoprotein E, are ligands of ApoER2 and VLDLR, these receptors are of interest with respect to Alzheimer’s disease. We will focus this review on the complex structure of ApoER2 and VLDLR and a recently characterized ligand, namely clusterin.

Genetic Base of Behavioral Disorders in Mucopolysaccharidoses: Transcriptomic Studies

“…However, further studies are required to learn about specific functions of SERPINE2/PN1, and possible connections of overexpression of SERPINE2 with symptoms occurring in MPS IX. The VLDLR, which is up-regulated in MPS IX, codes for a lipoprotein receptor family which bind apolipoprotein E [50]. Therefore, effects of dysregulation of VLDLR expression in MPS might be assumed to be associated to those for APOE.…”

Selenoprotein P; P for Plasma, Prognosis, Prophylaxis, and More

“…The excessively reductive environment in/around cells caused by overloaded SeP and/or the SeP-evoked overexpression of selenoproteins is proposed to suppress "signaling ROS" required for activation of the AMPK pathway and for the expression of PGC-1α, a master regulator of mitochondrial biogenesis. Interestingly, such a SeP-caused hypo-oxidative stress condition in skeletal muscle was found to abolish an exercise-triggered metabolic adaptation of muscles, 46) to which a coincidence of high blood SeP and obesity 58,[61][62][63] may be attributed.…”

“…To date, apolipoprotein E receptor 2 (ApoER2), megalin and low-density lipoprotein receptor-related protein 1 (LRP1), all of which are cell surface low density lipoprotein receptor (LDLR) family members, 42) have been identified as SeP receptors in mouse testis and brain, 43,44) kidney, 45) and human myoblasts, 46) respectively.…”

“…45) Meanwhile, some of these LDLR members may cooperatively form a coreceptor for SeP, as suggested by data that the small interfering RNA (siRNA)-mediated depletion of either LRP1 or ApoER2 in myoblasts resulted in a significant deficiency in SeP uptake (see below). 46) In vitro cell culture experiments showed that SeP can bind to multiple cell lines, and that SeP is incorporated into cells in a receptor dependent manner, probably via endocytosis, and thereby enhances the cellular expression of other selenoproteins by providing a source of Se. 46,50,51) The mechanism for Se recycling from SeP involves lysosomal SeP degradation, selenocysteine lyase (SCL)-dependent extrication of H 2 Se, and incorporation to tRNA [Ser]Sec , followed by newly synthesized selenoproteins.…”

“…46) In vitro cell culture experiments showed that SeP can bind to multiple cell lines, and that SeP is incorporated into cells in a receptor dependent manner, probably via endocytosis, and thereby enhances the cellular expression of other selenoproteins by providing a source of Se. 46,50,51) The mechanism for Se recycling from SeP involves lysosomal SeP degradation, selenocysteine lyase (SCL)-dependent extrication of H 2 Se, and incorporation to tRNA [Ser]Sec , followed by newly synthesized selenoproteins. 50,52) Of note, however, SeP-dependent Se delivery to cells in vitro should be carefully interpreted, given that mouse genetics clearly indicated predominant SeP-independent Se delivery to cells, as aforementioned.…”