Evidence map›Paper›PMID 22840771›Full record

ArticleChemistry & biology2012

Cellular uptake mechanisms and endosomal trafficking of supercharged proteins.

David B Thompson, Roberto Villaseñor, Brent M Dorr, Marino Zerial, David R Liu

Open access · greenAbstract read
In one paragraph

Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

53 citing papers in PubMed, 101 citations in OpenAlex.

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  17. Design rules for efficient endosomal escape.bioRxiv : the preprint server for biology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

David B ThompsonHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Roberto Villaseñor
Brent M Dorr
Marino Zerial
David R Liu
Howard Hughes Medical Institute · USMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

Expanding the Scope of Protein EvolutionR01GM065400 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2002 to 2010
$2.5M
New Approaches for the Delivery of Proteins and Nucleic Acids Into CellsR01GM095501 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2011 to 2014
$1.3M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM065400NIGMS NIH HHS R01GM065400NIGMS NIH HHS R01 GM095501
6 · The paper itself

Abstract

Supercharged proteins (SCPs) can deliver functional macromolecules into the cytoplasm of mammalian cells more potently than unstructured cationic peptides. Thus far, neither the structural features of SCPs that determine their delivery effectiveness nor their intracellular fate postendocytosis, has been studied. Using a large set of supercharged GFP (scGFP) variants, we found that the level of cellular uptake is sigmoidally related to net charge and that scGFPs enter cells through multiple pathways, including clathrin-dependent endocytosis and macropinocytosis. SCPs activate Rho and ERK1/2 and also alter the endocytosis of transferrin and EGF. Finally, we discovered that the intracellular trafficking of endosomes containing scGFPs is altered in a manner that correlates with protein delivery potency. Collectively, our findings establish basic structure-activity relationships of SCPs and implicate the modulation of endosomal trafficking as a determinant of macromolecule delivery efficiency.

Indexed as

EndocytosisEndosomesFluorescenceGreen Fluorescent ProteinsHeLa CellsHumansStructure-Activity RelationshipGreen Fluorescent Proteins

Identifiers

PMID22840771
PMCPMC3408882
OpenAlexW2135093868

What OpenQuestion holds

Textmetadata
LicenceTDM
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.