Inhibition by Cytosolic Acidification

Acidification of the cytosol to a pH below 6.5 strongly reduces the endocytic uptake of transferrin or EGF. However, the number of binding sites for transferrin is not reduced, nor is the number of coated pits. The apparent molecular reason for the observed inhibition of internalization is that coated vesicles are unable to pinch off from the plasma membrane, although they are assembled correctly (Heuser 1989; Sandvig et al. 1987). Thus, cytosolic acidification prevents endocytosis by paralyzing clathrin lattices that remain attached to the plasma membrane. Under these conditions, adaptors including AP-2 remain aggregated at the plasma membrane and associated with receptors (Sorkin and Carpenter 1993; Hansen et al. 1993). Negative side effects of cytosol acidification on cell physiology are to be expected, but have not been investigated in detail.

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