Disease relevance of LRP1

• The low density lipoprotein receptor-related protein (LRP) is responsible for the clearance of several physiological ligands including a complex of proteinase and alpha2-macroglobulin (alpha2M) and for the entrance of Pseudomonas exotoxin A (PEA) into cells [1].

High impact information on LRP1

• These data suggest that deletion of large internal portions of LRP, including the processing site, does not prevent transport of LRP to the plasma membrane, nor does it abolish the interaction of LRP with alpha2M* or PEA [1].
• However, the exit of mutant LRP from the endoplasmic reticulum was retarded by the Arg3942-to-Ser substitution, as evidenced by prolonged retention within the endoplasmic reticulum (t1/2 = 4 h for LRP-wt and t1/2 > 13 h for LRP-RS) [2].
• Transfection of the mutant LRP (designated LRP-RS) into a Chinese hamster ovary cell line lacking endogenous LRP resulted in expression of the unprocessed full-length proreceptor [2].
• We have prepared expression plasmids for the full-length chicken LRP (designated LRP100) and two intermediates encoding 25 and 67% of the receptor (designated LRP25 and LRP67, respectively) using overlapping cDNA fragments [1].
• Sorting of LRP from the endosomal compartment to lysosomes or recycling to the plasma membrane were also unaltered in mutant LRP-RS [2].

Chemical compound and disease context of LRP1

• Comparison of cell lines stably expressing either the wild-type LRP (LRP-wt) or the unprocessed LRP-RS showed that at comparable expression levels, both receptors restored the sensitivity of cellular protein synthesis to Pseudomonas exotoxin A (IC50 = 25 ng/ml) [2].

Biological context of LRP1

• The results indicate that avian LRP/alpha 2MR genes have emerged from an ancestor designed to ensure a pivotal event in the reproduction of oviparous species, i.e. vitellogenesis, and that mammalian LRP/alpha 2MRs have acquired features required for functioning in plasma clearance of certain non-yolk proteins [3].

Anatomical context of LRP1

• This chicken protein is expressed in somatic tissues and is different from a second LRP/alpha 2MR exclusively expressed in growing ovarian follicles [3].
• Subcellular fractionation and neuraminidase treatment showed that both LRP forms were transported to the plasma membrane [2].
• Stable transformants of LRP100, LRP67, and LRP25 were generated in a mutant Chinese hamster ovary cell line that lacked expression of endogenous LRP and was resistant to PEA [1].
• Pulse-chase analysis showed that the lack of processing of LRP had no effect on the stability of its post-endoplasmic reticulum form or on the rate of its intracellular transit from the endoplasmic reticulum to the Golgi apparatus [2].

Associations of LRP1 with chemical compounds

• Furthermore, expression of the three LRP variants restored, to various degrees, sensitivity to PEA and the ability to degrade methylamine-activated alpha2M (alpha2M*) [1].

References