GANGLIOSIDE-MODULATED PROTEOLYSIS BY CA-2+-ACTIVATED NEUTRAL PROTEINASE (CANP) - A ROLE OF GLYCOCONJUGATES IN CANP REGULATION

Abstract: We examined ganglioside modulation of the activity of the millimolar Ca2+‐sensitive form (mCANP) of calcium‐activated neutral proteinase (CANP), which is enriched in myelin, from brain. GM1, GD1a, GT1a, GM2, and GM4 produced a concentration‐dependent increase of mCANP activity. GD1a stimulated the greatest increase of enzyme activity (107%), followed by GT1a, whereas GD1b was inhibitory (56%). GM1, GM2, and GM4 stimulated but less so than GD1a and GT1a. Free N‐acetylneuraminic acid, asialo‐GM1, GM3, and a ganglioside mixture containing GM1, GD3, GD1a, and GD1b had no effect. The ganglioside‐mediated modulation was not affected by trifluoperazine and chlorpromazine (phospholipid‐binding antagonists). The mCANP Ca2+ requirement was significantly reduced in the presence of stimulatory gangliosides, and this increased sensitivity varied (10–50‐fold) with ganglioside structure. Gangliosides may interact with membrane mCANP and modulate its proteolytic action. Copyright © 1990, Wiley Blackwell. All rights reserved