ROLE OF CLATHRIN-COATED VESICLES IN GLYCOPROTEIN TRANSPORT FROM THE CELL-SURFACE TO THE GOLGI-COMPLEX

Plasma membrane glycoproteins recycle to the Golgi complex, but the ro ute followed by these proteins is not known. To elucidate the pathway of transport, the involvement of clathrin-coated vesicles was tested. This was accomplished by comparing the traffic of wild type low densit y lipoprotein receptor (LDLR) and FEZ 683, a mutant receptor whose end ocytosis from the cell surface in coated vesicles is reduced by 90-95% . Wild type LDLR traveled from the cell surface to the sialyltransfera se compartment of the Golgi with a half-time of 2.5 h in K562 human le ukemia cells expressing receptor from a transfected cDNA. In contrast, FH 683 LDLR recycled to the Golgi at 33% of the wild type rate, sugge sting that wild type LDLR is largely transported to the Golgi by a pat hway that involves clathrin-coated vesicles. Moreover, because clathri n coated vesicles that bud from the plasma membrane are transported to endosomes, surface-to-Golgi transport probably involves an endosomal intermediate. Finally, because there was substantial transport of muta nt LDLR to the Golgi even though its endocytosis in coated vesicles wa s greatly reduced, there may be a second pathway of surface-to-Golgi t raffic. Our results suggest that wild type LDLR may move from plasma m embrane to Gels by two routes. Two-thirds of the traffic proceeds via a coated vesicle-mediated pathway while the remainder may follow a cla thrin-independent pathway.