title: Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Umasankar
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sanker
authors.forename: James R
authors.initials: JR
authors.lastname: Thieman
authors.forename: Souvik
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Beverly
authors.initials: B
authors.lastname: Wendland
authors.forename: Michael
authors.initials: M
authors.lastname: Tsang
authors.forename: Linton M
authors.initials: LM
authors.lastname: Traub
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000502:physiology*; D019521:Body Patterning; D002966:Clathrin / Q000378:metabolism*; D047108:Embryonic Development; D004705:Endocytosis; D050556:Fatty Acid-Binding Proteins; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D033962:Adaptor Protein Complex 2; D002966:Clathrin; C524557:FCHO1 protein, human; C497031:FCHO2 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D011506:Proteins