# Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces

https://mdr.nims.go.jp/datasets/e82cd512-fb9c-429c-986e-d7685e43c76e

## File

- [Manuscript_12.docx](https://mdr.nims.go.jp/filesets/a0efb844-787f-4fdd-a81d-ac2872314625/download) ([Detail](https://mdr.nims.go.jp/filesets/a0efb844-787f-4fdd-a81d-ac2872314625.md))

## Id

e82cd512-fb9c-429c-986e-d7685e43c76e

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2025-03-27T04:04:43.258631Z

## Updated at

2025-03-27T08:44:09.962623Z

## Published at

2025-03-27T08:44:10.058918Z

## Doi

https://doi.org/10.48505/nims.5387

## First published url

https://doi.org/10.3390/cells14020138

## Date published

2025-01-17

## Recorded date published



## Resource type

journal_article

## Manuscript type

accepted_manuscript

## Collection



## Title

- title: Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That
    Is Reversibly Stretched and Contracted by Weak Forces
  title_type: original
  lang: en

## Description

- description: Nestin, a type VI intermediate filament protein, is well-known as neural
    stem cell marker protein. On the other hand, nestin specifically expressed in
    high-grade cancer cells and forms copolymerized filaments with vimentin. Our previous
    study has shown that nestin inhibits the binding of vimentin’s tail domain to
    actin microfilaments (AFs) by steric hin-drance with large nestin tail domain
    (NTD) of 170 kDa, thereby increasing the mobility of the three-dimensional network
    of the cytoskeleton, enhancing cell flexibility, and contrib-uting to cancer progression.
    In the course of the study, it was also discovered that nestin itself binds extremely
    stably to AFs via the NTD. This fact contradicts the mechanism de-scribed above.
    However, based on the further discovery that nestin binds to actin at the C-terminal
    end of NTD, we newly hypothesized that NTD forms a flexible cytoskeletal structure
    by extending with weak force. In vitro tensile tests using atomic force microscope
    were performed to assess the mechanical properties of NTDs to confirm the hypothesis.
    The C-terminus of the NTD was bound to the AFs by bringing the AFM tip modified
    with the NTD into contact with the AFs on the substrate. Tensile tests showed
    that the NTDs were elongated to a length corresponding to approximately 80% of
    their maximum length at weak forces of less than 150 pN. Furthermore, repeated
    tensile tests revealed that the NTD refolded quickly and behaved like a soft elastic
    material. Nestin stably binds to AFs and forms a three-dimensional network of
    the cytoskeleton, and the NTD extends with weak force and contracts quickly when
    the load is released. Thereby, it is suggested that nestin absorbs mechanical
    load on cells and plays a role in restoring the cytoskeleton.
  description_type: abstract
  lang: und

## Creator

- name: Ayana Yamagishi
  role: author
- name: Rina Tokuoka
  role: author
- name: Kazuki Imai
  role: author
- name: Mei Mizusawa
  role: author
- name: Moe Susaki
  role: author
- name: Koki Uchida
  role: author
- name: Saku T. Kijima
  role: author
  orcid: https://orcid.org/0000-0003-1080-6289
- name: Akira Nagasaki
  role: author
  orcid: https://orcid.org/0000-0002-1468-4592
- name: Daijiro Takeshita
  role: author
- name: Chiaki Yoshikawa
  role: author
  orcid: https://orcid.org/0000-0002-6589-387X
- name: Taro Q. P. Uyeda
  role: author
  orcid: https://orcid.org/0000-0002-3584-9499
- name: Chikashi Nakamura
  role: author
  orcid: https://orcid.org/0000-0002-8012-2192

## Contact agent



## Publisher

organization: MDPI AG

## Managing organization



## Keyword

- subject: Actin
  schema: not_defined
- subject: AFM
  schema: not_defined
- subject: Intermediate filament
  schema: not_defined
- subject: Nestin
  schema: not_defined

## Rights

- identifier: https://creativecommons.org/licenses/by/4.0/

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo



## Journal

- title: Cells
  issn: '20734409'
  volume: '14'
  issue: '2'
  article_number: '138'

## Conference



## Related item



## Funding

- identifier: 20H02533
  funder_name: Japan Society for the Promotion of Science
- identifier: 23H02452
  funder_name: Japan Society for the Promotion of Science

## Instrument



## Instrument operator



## Instrument managing organization



## Measurement method



## Specimen



## Chemical composition



## Structure for specimen



## Structural feature for specimen



## Specific property for specimen



## Process for specimen treatment



## Computational method



## Energy level/transition state



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## Custom property



## Fileset

- id: a0efb844-787f-4fdd-a81d-ac2872314625
  filename: Manuscript_12.docx
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  size: 13487430
  md5: 0f038c55c8920eb7e66815cea3c8a9f3

## Thumbnail

fileset_id: a0efb844-787f-4fdd-a81d-ac2872314625
filename: Manuscript_12.docx