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Cited by 115Cellular transport and secretionBiotin and Related StudiesCaveolin-1 and cellular processes

Transient Fcho1/2⋅Eps15/R⋅AP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding

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Ma, Li, Umasankar, Perunthottathu K., Wrobel, Antoni G., Lymar, Anastasia, McCoy, Airlie J., Holkar, Sachin S., Jha, Anupma, Pradhan-Sundd, Tirthadipa +3 more·2016·Developmental Cell
DOI 10.1016/j.devcel.2016.05.003PMC PMC4921775
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Abstract

Clathrin-coated vesicles form by rapid assembly of discrete coat constituents into a cargo-sorting lattice. How the sequential phases of coat construction are choreographed is unclear, but transient protein-protein interactions mediated by short interaction motifs are pivotal. We show that arrayed Asp-Pro-Phe (DPF) motifs within the early-arriving endocytic pioneers Eps15/R are differentially decoded by other endocytic pioneers Fcho1/2 and AP-2. The structure of an Eps15/R⋅Fcho1 μ-homology domain complex reveals a spacing-dependent DPF triad, bound in a mechanistically distinct way from the mode of single DPF binding to AP-2. Using cells lacking FCHO1/2 and with Eps15 sequestered from the plasma membrane, we establish that without these two endocytic pioneers, AP-2 assemblies are fleeting and endocytosis stalls. Thus, distinct DPF-based codes within the unstructured Eps15/R C terminus direct the assembly of temporary Fcho1/2⋅Eps15/R⋅AP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.

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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 [56]

    The Discussion (page unavailable) proposes that Eps15 oligomers engage multiple AP-2 adaptors to form nanoclusters, and describes polymeric clathrin in coat assembly. The Results, ‘A μHD Interaction Network’ (page unavailable), identify intersectin 1 as an FCHO1 binding partner. These passages support coat-component clustering, but do not establish that every listed scaffold both self-interacts and binds clathrin adaptors to produce it. (LLM, conf=0.84)

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Cited by

Sorted by citations

  • Insights of Endocytosis Signaling in Health and Disease

    Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59 · see citing works

    “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].”
    Background

Authors
Ma, L., Umasankar, P. K., Wrobel, A. G., Lymar, A., McCoy, A. J., Holkar, S. S., Jha, A., Pradhan-Sundd, T., Watkins, S. C., Owen, D. J., & Traub, L. M.
Affiliations
  • University of Pittsburgh (US)
  • University of Cambridge (GB)
Corresponding author
Traub, Linton M.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2016-06
Volume
37
Issue
5
Pages
428-443
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2016.05.003
PMC
PMC4921775
OpenAlex
W2399726023
Cited by
115
References
1
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 25 · 2022: 17 · 2021: 10 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 7 · 2016: 4
FWCI
8.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • NIH (R01 GM106963)
  • Wellcome Trust (090909/Z, 097040, 100140)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
clathrin-coated vesicles, AP-2, protein-protein interaction, endocytosis, cargo binding, ternary complex, interdomain linker
MeSH terms
Protein Domains, Amino Acid Sequence, Animals, Clathrin, Endocytosis, HeLa Cells, Humans, Membrane Proteins, Models, Biological, Models, Molecular, Protein Binding, Transfection, Amino Acid Motifs, Clathrin-Coated Vesicles, Adaptor Protein Complex 2, Adaptor Proteins, Signal Transducing, Fatty Acid-Binding Proteins, Rats, Protein Interaction Maps

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