P-Type Lectins

Lysosomes are intracellular membrane-bound organelles that turn over and degrade many types of macromolecules, via the action of lysosomal enzymes (also called acid hydrolases because of the low-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, they are segregated from other glycoproteins and selectively delivered to lysosomes. In most “higher” animal cells, this specialized trafficking is achieved primarily through the recognition of N-glycans containing mannose 6-phosphate (M6P) by “P-type” lectins. As the first clear-cut example of a biological role for glycans on mammalian glycoproteins and the first shown link between glycoprotein biosynthesis and human disease, the interesting history of its discovery is described in some detail. More recent data on other proteins with “P-type” lectin domains are also mentioned.