Lysosomes are intracellular membrane-bound organelles that perform the final degradation of many cellular macromolecules. This is achieved by the action of a number of lysosomal enzymes (originally called “acid hydrolases” because of the low internal pH characteristic of lysosomes). These enzymes are synthesized in the endoplasmic reticulum (ER) on membrane-bound ribosomes and traverse the ER-Golgi pathway along with other newly synthesized proteins. At the terminal Golgi compartment (the trans-Golgi network or TGN), they are segregated from all other glycoproteins and selectively delivered to lysosomes. In most “higher” animal cells, this specialized trafficking is achieved primarily by a specific glycan marker that is recognized by certain receptors. This chapter describes the discovery and characterization of this glycan-mediated biological system, which relies on recognition of glycans containing mannose-6-phosphate (M6P) by “P-type” lectins. This was the first clear-cut example of a biological role for glycans on mammalian glycoproteins and the first demonstrated link between glycoprotein biosynthesis and human disease. The interesting history of its discovery is therefore described in some detail.
Copyright © 2009, The Consortium of Glycobiology Editors, La Jolla, California.