Evidence map›Paper›PMID 28003333›Full record

ArticleThe Journal of cell biology2017

Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2.

Zuzana Kadlecova, Stephanie J Spielman, Dinah Loerke, Aparna Mohanakrishnan, Dana Kim Reed, Sandra L Schmid

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 198 citations in OpenAlex.

  1. Review
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  6. VAMP8 function reveals tight linkage between endocytic recycling and endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Review
  8. Review
  9. Review
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  11. Article
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  17. Uptake and Toxicity of Polystyrene NPs in Three Human Cell Lines.International journal of molecular sciences · 2025
    Article
  18. Article
  19. Article
  20. Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Zuzana KadlecovaDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Stephanie J SpielmanInstitute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122.
Dinah LoerkeDepartment of Physics and Astronomy, University of Denver, Denver, CO 80208.
Aparna MohanakrishnanDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Dana Kim ReedDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.ORCID http://orcid.org/0000-0002-3980-4239
Sandra L SchmidDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 sandra.schmid@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-1690-7024
The University of Texas Southwestern Medical Center · USTemple University · USUniversity of Denver · US

Funding

Request for administrative supplement to Parent R01 GM073165 entitled "Mechanisms regulating clathrin-mediated endocytosis"R01GM073165 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI METTLEN, MARCEL BERNARD · 2006 to 2022
$6.8M
The Clathrin Coated Vesicle CycleR01MH061345 · NIMH · UT SOUTHWESTERN MEDICAL CENTER · PI SCHMID, SANDRA L. · 2010 to 2019
$5.0M
THE CLATHRIN COATED VESICLE CYCLER37MH061345 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI SCHMID, SANDRA L. · 2000 to 2009
$4.7M
NIGMS NIH HHS R01 GM073165NIMH NIH HHS R01 MH061345NIMH NIH HHS R37 MH061345
6 · The paper itself

Abstract

The critical initiation phase of clathrin-mediated endocytosis (CME) determines where and when endocytosis occurs. Heterotetrameric adaptor protein 2 (AP2) complexes, which initiate clathrin-coated pit (CCP) assembly, are activated by conformational changes in response to phosphatidylinositol-4,5-bisphosphate (PIP2) and cargo binding at multiple sites. However, the functional hierarchy of interactions and how these conformational changes relate to distinct steps in CCP formation in living cells remains unknown. We used quantitative live-cell analyses to measure discrete early stages of CME and show how sequential, allosterically regulated conformational changes activate AP2 to drive both nucleation and subsequent stabilization of nascent CCPs. Our data establish that cargoes containing Yxxφ motif, but not dileucine motif, play a critical role in the earliest stages of AP2 activation and CCP nucleation. Interestingly, these cargo and PIP2 interactions are not conserved in yeast. Thus, we speculate that AP2 has evolved as a key regulatory node to coordinate CCP formation and cargo sorting and ensure high spatial and temporal regulation of CME.

Indexed as

EndocytosisAdaptor Protein Complex 2Adaptor Protein Complex alpha SubunitsAdaptor Protein Complex mu SubunitsAmino Acid MotifsCell LineClathrinClathrin-Coated VesiclesCoated Pits, Cell-MembraneHumansPhosphatidylinositol 4,5-DiphosphateProtein BindingProtein ConformationProtein Serine-Threonine KinasesProtein StabilityProtein TransportAAK1 protein, humanAdaptor Protein Complex 2adaptor protein complex 2, alpha 2 subunitadaptor protein complex 2, mu 1 subunitAdaptor Protein Complex alpha SubunitsAdaptor Protein Complex mu SubunitsClathrinPhosphatidylinositol 4,5-DiphosphateProtein Serine-Threonine Kinases

Identifiers

PMID28003333
PMCPMC5223608
OpenAlexW2568848023

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.