A Receptor for the Selective Uptake and Degradation of Proteins by Lysosomes

Ana María Cuervo, J. Fred Dice

Science · 1996 · 953 citations · 11 references

Concepts

TL;DR

Cells employ multiple protein degradation pathways, including a selective lysosomal import route that targets specific cytosolic proteins for degradation. Substrates of this pathway bind to the cytosolic tail of the 96‑kDa lysosomal membrane protein LGP96, as demonstrated in two distinct binding assays. LGP96 was identified as the receptor mediating selective lysosomal protein import, and its overexpression in Chinese hamster ovary cells markedly increases lysosomal proteolytic activity both in vivo and in vitro.

Abstract

Multiple pathways of protein degradation operate within cells. A selective protein import pathway exists for the uptake and degradation of particular cytosolic proteins by lysosomes. Here, the lysosomal membrane glycoprotein LGP96 was identified as a receptor for the selective import and degradation of proteins within lysosomes. Specific substrates of this proteolytic pathway bound to the cytosolic tail of a 96-kilodalton lysosomal membrane protein in two different binding assays. Overexpression of human LGP96 in Chinese hamster ovary cells increased the activity of the selective lysosomal proteolytic pathway in vivo and in vitro.

References

11