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Effects of brefeldin A on the endocytic route. Redistribution of mannose 6-phosphate/insulin-like growth factor II receptors to the cell surface.

1991; Elsevier BV; Volume: 266; Issue: 36 Linguagem: Inglês

10.1016/s0021-9258(18)54303-9

1083-351X

Hanna Damke, Judith Klumperman, Kurt Von Figura, Thomas Braulke,

Carbohydrate Chemistry and Synthesis

The effect of brefeldin A (BFA) on the trafficking of the mannose 6-phosphate/insulin-like growth factor I1 receptor within the endocytic route was analyzed.Treatment with BFA induced a redistribution of the receptor to the cell surface and increased both the binding and internalization of ligands 2-4-fold.The effect of BFA was dose-and time-dependent and reversible.Determinations of transport rates showed that BFA increases the internalization rate and the externalization rate of the receptor.This implies that the higher surface concentration is due to higher concentrations of receptor at the intracellular sites from where they recycle to the cell surface.The effect of BFA was additive to the redistribution induced by insulin-like growth factors I and I1 and was observed in all human and rodent cell lines analyzed.BFA increased also the cell surface expression of the M, 46,000 mannose 6-phosphate receptor but not of the transferrin receptor.The results indicate that BFA interferes with the transport of mannose 6-phosphate receptors and affects the endocytosis of lysosomal enzymes by increasing the number of receptors available for recycling to the cell surface.Brefeldin A (BFA)' is an isoprenoid fungal metabolite that blocks the transport of secretory, membrane, and lysosomal proteins through the Golgi (1-5).The organization of the Golgi is rapidly and reversibly altered by a retrograde transport of proteins resident in the cis, mid, and trans Golgi to the endoplasmic reticulum (ER) (4, 6).Therefore, newly synthesized proteins accumulating in the ER can undergo carbohydrate processing reactions, which normally occur in the Golgi.The reports on the sensitivity of the trans Golgi network (TGN) to BFA are controversial and depend on the cell type and the TGN markers used (7-9).In order to examine the effects of BFA on proteins which function in the secretory pathway as well as in the endocytic