A heterotetrameric complex termed AP-3 is involved in signal-mediated
protein sorting to endosomal-lysosomal organelles. AP-3 has been propo
sed to be a component of a nonclathrin coat. In vitro binding assays s
howed that mammalian AP-3 did associate with clathrin by interaction o
f the appendage domain of its beta 3 subunit with the amino-terminal d
omain of the clathrin heavy chain. The beta 3 appendage domain contain
ed a conserved consensus motif for clathrin binding. AP-3 colocalized
with clathrin in cells as observed by immunofluorescence and immunoele
ctron microscopy. Thus, AP-3 function in protein sorting may depend on
clathrin.