Evidence map›Paper›PMID 27240195›Full record

ArticleNature biotechnology2016

A split horseradish peroxidase for the detection of intercellular protein-protein interactions and sensitive visualization of synapses.

Jeffrey D Martell, Masahito Yamagata, Thomas J Deerinck, Sébastien Phan, Carolyn G Kwa, Mark H Ellisman, Joshua R Sanes, Alice Y Ting

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
12.9field-weighted citation impact, top 1% 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

101 citing papers in PubMed, 177 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Construction of L-type lectin displaying Saccharomyces cerevisiae for Vibrio parahaemolyticus agglutination.International microbiology : the official journal of the Spanish Society for Microbiology · 2025
    Article
  13. Protein Engineering for Spatiotemporally Resolved Cellular Monitoring.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Comparison of two peroxidases with high potential for biotechnology applications - HRPComputational and structural biotechnology journal · 2024
    Article
  18. Article
  19. Review
  20. Article

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

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

8 authors at 4 institutions in 1 country.

Jeffrey D MartellDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Masahito YamagataDepartment of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.ORCID 0000-0001-8193-2931
Thomas J DeerinckNational Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California at San Diego, La Jolla, San Diego, California, USA.
Sébastien PhanNational Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California at San Diego, La Jolla, San Diego, California, USA.
Carolyn G KwaDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Mark H EllismanNational Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California at San Diego, La Jolla, San Diego, California, USA.
Joshua R SanesDepartment of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.
Alice Y TingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Massachusetts Institute of Technology · USHarvard University · USUniversity of California San Diego · USSalk Institute for Biological Studies · US

Funding

IVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9M
New Probe and Methods for Correlated LM & EMR01GM086197 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADAMS, STEPHEN ROY, BOASSA, DANIELA · 2008 to 2020
$8.3M
Synaptic Choices in the Retinotectal SystemR37NS029169 · NINDS · HARVARD UNIVERSITY · PI SANES, JOSHUA R · 2013 to 2019
$4.0M
Spatially-resolved proteomic mapping of living cellsR01CA186568 · NCI · STANFORD UNIVERSITY · PI TING, ALICE Y · 2013 to 2018
$3.3M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA186568NIGMS NIH HHS P41 GM103412NIGMS NIH HHS R01 GM086197NINDS NIH HHS R37 NS029169
6 · The paper itself

Abstract

Intercellular protein-protein interactions (PPIs) enable communication between cells in diverse biological processes, including cell proliferation, immune responses, infection, and synaptic transmission, but they are challenging to visualize because existing techniques have insufficient sensitivity and/or specificity. Here we report a split horseradish peroxidase (sHRP) as a sensitive and specific tool for the detection of intercellular PPIs. The two sHRP fragments, engineered through screening of 17 cut sites in HRP followed by directed evolution, reconstitute into an active form when driven together by an intercellular PPI, producing bright fluorescence or contrast for electron microscopy. Fusing the sHRP fragments to the proteins neurexin (NRX) and neuroligin (NLG), which bind each other across the synaptic cleft, enabled sensitive visualization of synapses between specific sets of neurons, including two classes of synapses in the mouse visual system. sHRP should be widely applicable to studying mechanisms of communication between a variety of cell types.

Indexed as

AnimalsHorseradish PeroxidaseMiceMicroscopy, ElectronMicroscopy, FluorescenceNerve Tissue ProteinsProtein EngineeringProtein Interaction MappingSynapsesHorseradish PeroxidaseNerve Tissue Proteins

Identifiers

PMID27240195
PMCPMC4942342
OpenAlexW2413994622

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.