Evidence map›Paper›PMID 21199870›Full record

ArticleThe Journal of biological chemistry2011

Single particle tracking confirms that multivalent Tat protein transduction domain-induced heparan sulfate proteoglycan cross-linkage activates Rac1 for internalization.

Junji Imamura, Yasuhiro Suzuki, Kohsuke Gonda, Chandra Nath Roy, Hiroyuki Gatanaga, Noriaki Ohuchi, Hideo Higuchi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Coreceptor functions of cell surface heparan sulfate proteoglycans.American journal of physiology. Cell physiology · 2022
    Review
  4. Amyloid Beta Is InternalizedFrontiers in molecular neuroscience · 2022
    Article
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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

7 authors at 4 institutions in 2 countries.

Junji ImamuraDepartment of Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Yasuhiro Suzuki
Kohsuke Gonda
Chandra Nath Roy
Hiroyuki Gatanaga
Noriaki Ohuchi
Hideo Higuchi
Tohoku University · JPNational Centre for Infectious Diseases · SGSaitama International Medical Center · JPTokyo University of Science · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mechanism by which HIV-1-Tat protein transduction domain (TatP) enters the cell remains unclear because of an insufficient understanding of the initial kinetics of peptide entry. Here, we report the successful visualization and tracking of TatP molecular kinetics on the cell surface with 7-nm spatial precision using quantum dots. Strong cell binding was only observed with a TatP valence of ≥8, whereas monovalent TatP binding was negligible. The requirement of the cell-surface heparan sulfate (HS) chains of HS proteoglycans (HSPGs) for TatP binding and intracellular transport was demonstrated by the enzymatic removal of HS and simultaneous observation of two individual particles. Multivalent TatP induces HSPG cross-linking, recruiting activated Rac1 to adjacent lipid rafts and thereby enhancing the recruitment of TatP/HSPG to actin-associated microdomains and its internalization by macropinocytosis. These findings clarify the initial binding mechanism of TatP to the cell surface and demonstrate the importance of TatP valence for strong surface binding and signal transduction. Our data also shed light on the ability of TatP to exploit the machinery of living cells, using HSPG signaling to activate Rac1 and alter TatP mobility and internalization. This work should guide the future design of TatP-based peptides as therapeutic nanocarriers with efficient transduction.

Indexed as

Signal TransductionHeLa CellsHeparan Sulfate ProteoglycansHIV-1HumansKineticsMembrane MicrodomainsPinocytosisProtein Structure, TertiaryProtein Transportrac1 GTP-Binding Proteintat Gene Products, Human Immunodeficiency VirusHeparan Sulfate Proteoglycansrac1 GTP-Binding ProteinRAC1 protein, humantat Gene Products, Human Immunodeficiency Virus

Identifiers

PMID21199870
PMCPMC3060510
OpenAlexW1996346894

What OpenQuestion holds

Textmetadata
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.