Secretory carrier membrane proteins (SCAMPs) are ubiquitous components of r
ecycling vesicles that shuttle between the plasma membrane, endosomes, and
the trans-Golgi complex. SCAMPs contain multiple N-terminal NPF repeats and
four highly conserved transmembrane regions. NPF repeats often interact wi
th EH domain proteins that function in budding of transport vesicles from t
he plasma membrane or the Golgi complex. We now show that the NPF repeats o
f SCAMP1 bind to two ER domain proteins, intersectin 1, which is involved i
n endocytic budding at the plasma membrane, and gamma-synergin, which may m
ediate the budding of vesicles in the trans-Golgi complex. Expression of SC
AMP1 lacking the N-terminal NPF repeats potently inhibited transferrin upta
ke by endocytosis, Our data suggest that one of the functions of SCAMPs is
to participate in endocytosis via a mechanism which may involve the recruit
ment of clathrin coats to the plasma membrane and the trans-Golgi network.