Evidence map›Paper›PMID 41360804›Full record

ArticleNature communications2025

Efficient cellular transformation via protein delivery through the protrusion-derived extracellular vesicles.

Toshifumi Fujioka, Tamako Nishimura, Hiroki Kawana, Koichiro M Hirosawa, Renta Yamakawa, Hani Sapili, Kayoko Oono-Yakura, Ryoya Nakagawa, Takanari Inoue, Osamu Nureki and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Extracellular Vesicles and Their Role in Osteogenesis.Bioengineering (Basel, Switzerland) · 2026
    Review
  3. Article
  4. Article
  5. Extracellular vesicles inEXO : beyond the cell · 2026
    Article
  6. Review
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

12 authors.

Toshifumi FujiokaDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Tamako NishimuraDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan. tnishimura@bs.naist.jp.ORCID http://orcid.org/0000-0001-9015-377X
Hiroki KawanaDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Koichiro M HirosawaInstitute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan.ORCID http://orcid.org/0000-0003-0170-3755
Renta YamakawaDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Hani SapiliDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Kayoko Oono-YakuraDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan.
Ryoya NakagawaDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Takanari InoueDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7957-7624
Osamu NurekiDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0003-1813-7008
Kenichi G N SuzukiInstitute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan.ORCID http://orcid.org/0000-0002-8436-5757
Shiro SuetsuguDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan. suetsugu@bs.naist.jp.ORCID http://orcid.org/0000-0002-4612-0628

Funding

Decoding dynamic interplay between signaling and membranes in chemotaxis bymolecular actuatorsR35GM149329 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Takanari Inoue · 2023 to 2026
$2.8M
MEXT | Japan Science and Technology Agency (JST) JPMJFR2413MEXT | Japan Society for the Promotion of Science (JSPS) 24K09778MEXT | Japan Society for the Promotion of Science (JSPS) 25K22505MEXT | Japan Society for the Promotion of Science (JSPS) JP17K07427MEXT | Japan Society for the Promotion of Science (JSPS) JP20H03252MEXT | Japan Society for the Promotion of Science (JSPS) JP20K06625MEXT | Japan Society for the Promotion of Science (JSPS) JP20KK0341MEXT | Japan Society for the Promotion of Science (JSPS) JP21H05047MEXT | Japan Society for the Promotion of Science (JSPS) JP23H02476MEXT | Japan Society for the Promotion of Science (JSPS) JP24H01286MEXT | JST | Core Research for Evolutional Science and Technology (CREST) JPMJCR1863MEXT | JST | Core Research for Evolutional Science and Technology (CREST) JPMJCR24B3NIGMS NIH HHS R35 GM149329NSF | BIO | Division of Molecular and Cellular Biosciences (MCB) 000819255U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM149329
6 · The paper itself

Abstract

Extracellular vesicles (EVs) mediate the transfer of intracellular proteins from producer to recipient cells. EVs originate either from plasma membrane protrusions or endosomes, with endosome-derived EVs being extensively studied and engineered. However, the efficiency and functionality of protein transfer via both types of EVs remain poorly understood. Here, we demonstrate that natural EVs derived from cell protrusions dependent on the I-BAR protein MIM, rather than from endosomes, deliver the functional small GTPase Rac1 protein at levels similar to microinjection. Rac1-containing EVs are internalized via endocytosis, trafficked through endosomal compartments, and subsequently released into the cytosol, where they enhance cell motility. To evaluate broader applicability, the genome-editing protein Cas12f is packaged into protrusion-derived EVs by MIM and endosome-derived EVs by endosomal tetraspanin CD63. Notably, protrusion-derived EVs deliver Cas12f with significantly higher efficiency than endosome-derived EVs, highlighting their superior capability for functional protein transfer. Our findings establish the protrusion-derived EVs as a powerful platform for the efficient and bioactive delivery of both native and engineered proteins, expanding the EV-based therapeutic strategies.

Indexed as

Extracellular Vesiclesrac1 GTP-Binding ProteinAnimalsCell MovementEndocytosisEndosomesHEK293 CellsHumansProtein TransportTetraspanin 30CD63 protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanTetraspanin 30

Identifiers

PMID41360804
PMCPMC12686433

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.