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Cited by 94Cellular transport and secretionDevelopmental Biology and Gene RegulationBiotin and Related Studies

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

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Umasankar, P. K., Sanker, Subramaniam, Thieman, James R., Chakraborty, Souvik, Wendland, Beverly, Tsang, Michael, Traub, Linton M.·2012·Nature Cell Biology
DOI 10.1038/ncb2473PMC PMC3354769
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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.

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  • Scaffolds such as EPS15, clathrin, intersectins, and EPS15R interact with themselves and with clathrin adaptors to cluster coat components together.

    “The scaffolds such as epidermal growth factor receptor substrate 15 (EPS15), clathrin, intersectins, and epidermal growth factor receptor substrate 15 like 1 (EPS15R) interact with themselves and with the clathrin adaptors to cluster the coat components together [43,55,56].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [43]

    The Results (‘The FCHO endocytic hub’; page not provided) show that EPS15, EPS15R and intersectin associate with the FCHO1 endocytic hub, and that EPS15 and intersectin bind an AP-2 appendage. The Introduction describes clathrin assembly and interactions that initiate coat formation. The copy does not establish that every listed scaffold interacts with itself and with clathrin adaptors to cluster coat components. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Receptor-mediated endocytosis is a highly regulated cellular process for internalization of various macromolecules including viral protein, toxins, metabolites, protein growth factors (EGF, PDGF), and polypeptide hormones such as insulin and luteinizing hormone.

    “Further, it is a highly regulated cellular process for internalization of various macromolecules including viral protein, toxins, metabolites, protein growth factors (EGF, PDGF), and polypeptide hormones, such as insulin and luteinizing hormone [41,42,43].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [43]

    The Introduction (page unavailable) describes clathrin-mediated endocytosis as selective internalization of cell-surface components and extracellular macromolecules, with sorting signals governing cargo capture. The Discussion (page unavailable) addresses receptor uptake in BMP signaling. Our copy does not identify viral proteins, toxins, metabolites, EGF, PDGF, insulin, or luteinizing hormone as cargo, so the specific list is unsupported by this source. (LLM, conf=0.86)

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Cited by

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Authors
Umasankar, P. K., Sanker, S., Thieman, J. R., Chakraborty, S., Wendland, B., Tsang, M., & Traub, L. M.
Affiliations
  • University of Pittsburgh (US)
  • Johns Hopkins University (US)
Corresponding author
Traub, Linton M.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2012-04-08
Volume
14
Issue
5
Pages
488-501
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb2473
PMC
PMC3354769
OpenAlex
W1982116050
Cited by
94
References
0
Citations by year
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FWCI
5.15
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL088016)
  • National Institute of General Medical Sciences (R01GM060979, R01 GM-60979)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 53249, R01DK053249)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
Keywords
clathrin-mediated endocytosis, AP-2, clathrin coat assembly, BMP signaling, dorsoventral patterning, zebrafish embryonic development, cargo recognition
MeSH terms
Clathrin, Endocytosis, HeLa Cells, Humans, Membrane Proteins, Proteins, Body Patterning, Gene Silencing, Adaptor Protein Complex 2, Embryonic Development, Fatty Acid-Binding Proteins

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