Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning

Clathrin-mediated endocytosis occurs at multiple independent import sites on the plasma membrane, but how these positions are selected and how different cargo is simultaneously recognized is obscure. FCHO1 and FCHO2 are early-arriving proteins at surface clathrin assemblies and are speculated to act as compulsory coat nucleators, preceding the core clathrin adaptor AP-2. Here, we show that the μ-homology domain of FCHO1/2 represents an endocytic interaction hub. Translational silencing of fcho1 in zebrafish embryos causes strong dorsoventral patterning defects analogous to Bmp signal failure. The Fcho1 μ-homology domain interacts with the Bmp receptor Alk8, uncovering an endocytic component that positively modulates Bmp signal transmission. Still, the fcho1 morphant phenotype is distinct from severe embryonic defects apparent when AP-2 is depleted. Our data thus challenge the primacy of FCHO1/2 in coat initiation. Clathrin-mediated endocytosis requires the coordinated spatial and temporal recruitment of adaptor, sorting and cargo proteins. Traub and colleagues investigate this process during zebrafish development and report that the AP-2 adaptor protein complex has a key, early role in clathrin-coated bud formation. Fcho1/2, though necessary for proper development, seems to act downstream of AP-2.