Three clathrin-dependent budding steps and cell polarity.

Clathrin plays an important role in the vesicular transport of proteins in all eukaryotes, but the precise steps in which it is involved may not be identical in all of them. Here, I put forward the hypothesis that three distinct clathrin-dependent budding events are common to all eukaryotes and have the following distinctive features: the first requires actin, the second is used for targeting soluble hydrolases from the Golgi to the hydrolytic compartment, and the third uses a tyrosine localization signal to concentrate membrane proteins. I suggest that the latter budding step is found on endosomes in yeast and is used for retrieval of membrane proteins back to the Golgi. Several testable predictions arise from this hypothesis as well as a possible evolutionary scenario concerning the origin of basolateral and apical plasma membranes in multicellular organisms.