Carbohydrate mediated recognition of lysosomal enzymes by cell surface receptors

Abstract

The recognition of lysosomal enzymes by various carbohydrate specific cell surface receptors is reviewed. In particular the biosynthesis of mannose 6-phosphate residues in lysosomal enzymes and their role for targeting of lysosomal enzymes to lysosomes are discussed. Most of the lysosomal enzymes that have been assayed for are glycoproteins (Strawser and Touster, 1980). Among the physiological functions ascribed to the carbohydrate moiety in lysosomal enzymes, were a possible contribution to the catalytic activity and stability towards lysosomal proteases. At present no example is kown in which the catalytic activity of a lysosomal enzyme was shown to depend on its carbohydrate moiety. In contrast, removal or modification of the carbo- hydrate, had no effect on the catalytic properties of the lysosomal enzymes so far studied. Lysosomal enzymes display a considerable stability towards various pro- teinases. It is, however, not known to what extent the carbohydrate moiety contri- butes to the stability of lysosomal enzymes in their physiological environment. Several examples of non lysosomal glycoproteins are known in which oligosac- charides seem to function in stabilizing the polypeptides (Gibson et al., 1980). In the past ten years it became evident that the carbohydrate moiety in lysosomal enzymes is of importance for the transfer of lysosomal enzymes into lysosomes. A variety of cells expose on their surface receptors that recognize the carbohydrate part of lysosomal enzyme and transfer the receptor bound lysosomal enzymes into lysosomes or related structures. Most of the receptors have been isolated and characterized (Neufeld and Ashwell, 1980). In table 1 the carbohydrate specific receptors mediating endocytosis of lyso- somal enzymes are listed up along with the cell types where they have been identi- fied. The receptors specific for galactose/N-acetylgalactosamine, mannose/ N-acetylglucosamine or L-fucose residues in glycoproteins are not specific for lysosomal enzymes, and it is not clear at present whether they mediate the trans- fer of lysosomal enzymes under normal conditions. The recognition of lysosomal enzyme via mannose 6-phosphate specific recap- tors has gained special interest. Hickman and Neufeld (1972) had shown that genetic deficiency of a recognition marker in lysosomal enzymes from I-cell (mucolipidosis II) fibroblasts is accompanied by loss of newly synthesized lyso- somal enzymes into the medium and intracellular deficiency of thse enzymes (II).