Evidence map›Paper›PMID 41366027›Full record

ArticleCommunications biology2025

Elevated SUN1 promotes migratory cell polarity defects through mechanically coupling microtubules to the nuclear lamina.

Yutao Li, Yicong Zhang, Mengqi Chen, Susumu Antoku, Junjun Ding, Kaiyao Huang, Gregg G Gundersen, Wakam Chang

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

8 authors.

Yutao LiDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macau, China.
Yicong ZhangDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macau, China.
Mengqi ChenDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macau, China.
Susumu AntokuDepartment of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Junjun DingCenter for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, China.ORCID http://orcid.org/0000-0002-9936-882X
Kaiyao HuangKey Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Gregg G GundersenDepartment of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Wakam ChangDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macau, China. wakamchang@um.edu.mo.ORCID http://orcid.org/0000-0003-4431-2033

Funding

Cytoskeleton, Nucleus and Integrin Recycling in Cell MigrationR35GM136403 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GUNDERSEN, GREGG G · 2020 to 2024
$3.3M
Nucleoskeleton-Cytoskeleton Connections and Cell Polarity in AgingR01AG064944 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GUNDERSEN, GREGG G, WORMAN, HOWARD J · 2019 to 2023
$2.5M
Fundo para o Desenvolvimento das Ciências e da Tecnologia (Science and Technology Development Fund) 0061/2022/AFundo para o Desenvolvimento das Ciências e da Tecnologia (Science and Technology Development Fund) 0077/2020/A2Fundo para o Desenvolvimento das Ciências e da Tecnologia (Science and Technology Development Fund) 0099/2022/AFJNational Natural Science Foundation of China (National Science Foundation of China) 32261160642NIA NIH HHS R01 AG064944NIGMS NIH HHS R35 GM136403
6 · The paper itself

Abstract

In migratory fibroblasts, front-rear polarity is defined by the centrosome positioned anterior to a rearward nucleus. To achieve this polarity, actin cables couple to nuclear membrane proteins nesprin-2G and SUN2 and drive the nucleus backward. Aging disrupts this polarity by increasing SUN1, a SUN2 homolog. Here, we investigated the molecular mechanisms behind this disruption and found that the dominant-negative effect of SUN1 and progerin, a lamin A variant, required direct SUN1-lamin A interaction. Microtubule interaction and force transmission through a nesprin, identified as nesprin-2, are crucial for SUN1's effect. We further discovered that stable microtubules are both necessary and sufficient to inhibit cell polarity. Using SUN1-SUN2 chimeric proteins, we demonstrated that the SUN domains determine their roles in cell polarization. Our findings reveal how elevated SUN1 disrupts cell polarity through coupling microtubules and nuclear lamina, emphasizing the impact of altered microtubule stability and nuclear mechanotransduction in polarity defects.

Indexed as

Cell MovementCell PolarityMembrane ProteinsMicrotubule-Associated ProteinsMicrotubulesNuclear LaminaNuclear ProteinsAnimalsFibroblastsHumansLamin Type AMiceTelomere-Binding ProteinsLamin Type AMembrane ProteinsMicrotubule-Associated ProteinsNuclear ProteinsSUN1 protein, humanSUN1 protein, mouseSun2 protein, mouseTelomere-Binding Proteins

Identifiers

PMID41366027
PMCPMC12765022

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.