AP2A1 modulates cell states between senescence and rejuvenation

Chantachotikul, Pirawan; Liu, Shiyou; Furukawa, Kana et al.

Cellular Signalling, 2025, 127, 111616

Number of Access:327（2025-07-18 14:21 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100573

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Title
AP2A1 modulates cell states between senescence and rejuvenation
Creator
CreatorName
Chantachotikul, Pirawan
CreatorName
Liu, Shiyou
NRID
1000070807461 1000070807461
researchmap permalink
1234_ 1234_
CreatorName
Furukawa, Kana
NRID
1000030379713 1000030379713
ORCID
0000-0002-0556-4599 0000-0002-0556-4599
researchmap permalink
read0138586 read0138586
Scopus Author ID
8645720800 8645720800
CreatorName
Deguchi, Shinji
Subject
AP2A1
Cell size control
Focal adhesions
Rejuvenation
Senescence
Stress fibers
Description
Chantachotikul P., Liu S., Furukawa K., et al. AP2A1 modulates cell states between senescence and rejuvenation. Cellular Signalling 127, 111616 (2025); https://doi.org/10.1016/j.cellsig.2025.111616.
Abstract
Aging proceeds with the accumulation of senescent cells in multiple organs. These cells exhibit increased size compared to young cells, which promotes further senescence and age-related diseases. Currently, the molecular mechanism behind the maintenance of such huge cell architecture undergoing senescence remains poorly understood. Here we focus on the reorganization of actin stress fibers induced upon replicative senescence in human fibroblasts, widely used as a senescent cell model. We identified, together with our previous proteomic study, that AP2A1 (alpha 1 adaptin subunit of the adaptor protein 2) is upregulated in senescent cells along the length of enlarged stress fibers. Knockdown of AP2A1 reversed senescence-associated phenotypes, exhibiting features of cellular rejuvenation, while its overexpression in young cells advanced senescence phenotypes. Similar functions of AP2A1 were identified in UV- or drug-induced senescence and were observed in epithelial cells as well. Furthermore, we found that AP2A1 is colocalized with integrin β1, and both proteins move linearly along stress fibers. With the observations that focal adhesions are enlarged in senescent cells and that this coincides with strengthened cell adhesion to the substrate, these results suggest that senescent cells maintain their large size by reinforcing their effective anchorage through integrin β1 translocation along stress fibers. This mechanism may work efficiently in senescent cells, compared with a case relying on random diffusion of integrin β1, given the enlarged cell size and resulting increase in travel time and distance for endocytosed vesicle transportation.
Publisher
Elsevier Inc.
Source Title
Cellular Signalling
Volume (Issue)
127
Page
111616
Date of Issued
2025-03-01
Language
English
Handle URL
https://hdl.handle.net/11094/100573
PISSN
08986568
eISSN
18733913
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1016/j.cellsig.2025.111616
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article