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PMID: 22484487 Published · epublish English Journal Article Research Support, N.I.H., Extramural

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

Nature cell biology ·Vol. 14 ·No. 5 ·2012-04-08 ·Pages 488-501

Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, Traub LM

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.

MeSH Terms
Adaptor Protein Complex 2/genetics,physiology Body Patterning Clathrin/metabolism Embryonic Development Endocytosis Fatty Acid-Binding Proteins Gene Silencing HeLa Cells Humans Membrane Proteins Proteins/genetics,physiology
Chemicals
Adaptor Protein Complex 2 Clathrin FCHO1 protein, human FCHO2 protein, human Fatty Acid-Binding Proteins Membrane Proteins Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Umasankar P K
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Sanker Subramaniam
Thieman James R
Chakraborty Souvik
Wendland Beverly
Tsang Michael
Traub Linton M
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2473
Published
2012-04-08
Epub
2012-00-08
Pages
488-501
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3354769
Subset
IM
Grants
NIDDK NIH HHS · R01 DK53249 · United States
NIDDK NIH HHS · R01 DK053249 · United States
NIGMS NIH HHS · R01 GM060979 · United States
NHLBI NIH HHS · R01 HL088016 · United States
NIGMS NIH HHS · R01 GM60979 · United States
Corrections
CommentIn
PMID: 22552146
External Links
PubMed source DOI: 10.1038/ncb2473 PMC Full Text View journal details
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