Coated vesicles had been described as early as 1961. These small membranous structures were characterized by a highly organized layer of material on the cytoplasmic surface, “but no one knew their function,” says Marilyn Farquhar, whose lab at the time had become interested in how the Golgi complex helped produce enzymes.

Roth and Porter (1964) had provided evidence that coated vesicles have specialized functions in the cellular uptake of proteins. But for Friend and Farquhar (1967), the simple idea of uptake was not enough. They helped cement the idea that cellular trafficking involved an intersecting set of cellular highways.

They demonstrated that cells contain different types of coated vesicles, and that these vesicles are not only involved in protein uptake but also in the transport of lysosomal enzymes. The two pathways converged in multivesicular bodies (now known as endosomes), explaining how proteins could be endocytosed and then processed by cellular enzymes. The processing, we now know, takes places only after endosomes have either matured into or sent vesicles to lysosomes.

graphic

Vesicles large (lv) and small (sv) deliver contents to the incipient lysosome.

FARQUHAR

The 1967 paper “was quite unique for its time,” says Farquhar, because the group used three labels: soluble horseradish peroxidase as a tracer for protein uptake; thiamine pyrophosphatase as a Golgi marker; and acid phosphatase as a lysosomal enzyme marker. Using this method her group was able to distinguish among different types of vesicles and follow their direction of movement during protein uptake.

One type of coated vesicle, which was larger in diameter, formed at the cell surface by pinocytic invagination of the apical cell membrane. It moved toward and fused with multivesicular bodies, thereby serving to transport endocytosed protein inside the cell. The other type of coated vesicle, smaller in size, seemed to originate from the Golgi cisternae and serve, at least in part, to transport the enzyme acid phosphatase and possibly other acid hydrolases from their site of packaging in the Golgi to multivesicular bodies, thus uniting the endocytosed and lytic proteins.

Since the small vesicles, which Farquhar refers to as “Golgi vesicles,” carry lytic enzymes, the authors concluded they correspond to primary lysosomes—particles that contain hydrolytic enzymes but have not yet participated in digestion. Today it is known that these so-called Golgi vesicles belong to the family of clathrin-coated vesicles. LB

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The Rockefeller University Press
2005