Biosynthesis of intestinal microvillar proteins. Role of the Golgi complex and microtubules.
The effect of monensin and colchicine on the biogenesis of aminopeptidase N (EC 3.4.11.2), aminopeptidase A (EC 3.4.11.7), dipeptidyl peptidase IV (EC 3.4.14.5), sucrase (EC 3.2.1.48)-isomaltase (EC 3.2.1.10) and maltase-glucoamylase (EC 3.2.1.20) was studied in organ-cultured pig small-intestinal explants. On the ultrastructural level, monensin (1 microM) caused an increasingly extensive dilation and vacuolization of the Golgi complex during 4h exposure of the explants. On the molecular level, the effect of monensin was twofold. (1) The processing from the initial high-mannose-glycosylated form to the mature complex-glycosylated form was arrested. For some of the enzymes studied, intermediate stages between the high-mannose and complex forms could be seen, probably corresponding to 'trimmed' or partially complex-glycosylated polypeptides. (2) Labelled microvillar enzymes failed to reach their final destination. These findings suggest the involvement of the Golgi complex in the post-translational processing and transport of microvillar enzymes. The presence in the growth medium of colchicine (50 micrograms/ml) caused a significant inhibition of the appearance of newly synthesized enzymes in the microvillar membrane during a 3 h labelling period. Since synthesis and post-translational modification of the microvillar enzymes were largely unaffected by colchicine, the results obtained suggest that microtubules play a role in the final transport of the enzymes from the Golgi complex to the microvillar membrane.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology; D008871:Microvilli / Q000201:enzymology; D008985:Monensin / Q000494:pharmacology; D009924:Organ Culture Techniques; D013552:Swine
D008985:Monensin; D003078:Colchicine