New Insights into the Endocytic Pathway

Abstract

Since 1983 our laboratory has carried out a series of studies on the endocytic pathway in epithelioid cells. In the initial work which described the uptake and recycling of transferrin receptors (TfnR) we identified the endosome as containing networks of branching tubular cisternae and vacuoles (Hopkins and Trowbridge 1983). A most important insight into function was provided by the finding that while a pulse of transferrin is internalised and recycled (t1/2 = 7 mins) continuous incubation brings about linear uptake for up to 40 mins. Later studies showed that the system to which transferrin has access is indeed large and widely distributed, extending from just below the plasma membrane into the pericentriolar area. Within the pericentriolar area the most prominent TfnR-containing elements are multivesicular bodies with long, often branching, tubular arms (Hopkins 1983). Subsequent studies showed that epidermal growth factor (EGF) induced EGFR to move through the full extent of this TfnR-containing system and to be delivered to the TfnR-negative lysosomes in the immediate vicinity of pericentriolar endosomal elements (Miller et al 1986). In collaboration with de Brabander we then used video microscopy to show that TfnR containing endosomes required an intact microtubular cytoskeleton to move from the peripheral cytoplasm to the pericentriolar area (de Brabander et al 1985).