Common signals control low density lipoprotein receptor sorting in endosomes and the Golgi complex of MDCK cells.

The cytoplasmic domain of the LDL receptor bears two tyrosine-containing determinants that can independently target receptors from the Golgi to the basolateral plasma membrane of MDCK cells. We found that these determinants, localized to the membrane-proximal and -distal regions of the receptor's cytoplasmic domain, also control polarized sorting in endosomes. Inactivation of the distal determinant reduced receptors' ability to return to the basolateral domain following endocytosis, resulting instead in receptor transcytosis from basolateral endosomes to the apical plasma membrane. Similarly, receptors internalized from the apical surface were transported from apical endosomes to the basolateral surface, owing to the proximal basolateral targeting determinant. Thus, receptor recycling in endosomes is directed by the same signals as polarized sorting in the Golgi, indicating that sorting on the endocytic and biosynthetic pathways involves similar mechanisms. The observation that brefeldin A interfered with sorting but not transport in both endosomes and the Golgi further supports this.