AP2A1 modulates cell states between senescence and rejuvenation

Chantachotikul, Pirawan; Liu, Shiyou; Furukawa, Kana; Deguchi, Shinji

doi:https://doi.org/10.1016/j.cellsig.2025.111616

AP2A1 modulates cell states between senescence and rejuvenation

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

Cellular Signalling, 2025, 127, 111616

アクセス数:327件（2025-07-18 10:16 集計）

固定URL: https://hdl.handle.net/11094/100573

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タイトル	AP2A1 modulates cell states between senescence and rejuvenation
著者	著者名 Chantachotikul, Pirawan
	著者名 Liu, Shiyou
	NRID 1000070807461 1000070807461 researchmap permalink 1234_ 1234_ 著者名 Furukawa, Kana
	NRID 1000030379713 1000030379713 ORCID 0000-0002-0556-4599 0000-0002-0556-4599 researchmap permalink read0138586 read0138586 Scopus Author ID 8645720800 8645720800 著者名 Deguchi, Shinji
キーワード等	AP2A1
	Cell size control
	Focal adhesions
	Rejuvenation
	Senescence
	Stress fibers
内容	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.
抄録	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.
出版者	Elsevier Inc.
収録物名	Cellular Signalling
巻(号)	127
ページ	111616
刊行年月	2025-03-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/100573
PISSN	08986568
eISSN	18733913
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.cellsig.2025.111616
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Cellular Signalling. 2025, 127, p. 111616
DC.title	AP2A1 modulates cell states between senescence and rejuvenation
DC.creator	Chantachotikul, Pirawan
	Liu, Shiyou
	Furukawa, Kana
	Deguchi, Shinji
DC.publisher	Elsevier Inc.
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-01
DC.identifier	https://doi.org/10.1016/j.cellsig.2025.111616
DC.subject	AP2A1
	Cell size control
	Focal adhesions
	Rejuvenation
	Senescence
	Stress fibers
DC.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.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	100573
citation_title	AP2A1 modulates cell states between senescence and rejuvenation
citation_author	Chantachotikul, Pirawan
	Liu, Shiyou
	Furukawa, Kana
	Deguchi, Shinji
citation_publisher	Elsevier Inc.
citation_language	英語
citation_date	2025-03-01
citation_journal_title	Cellular Signalling
citation_volume	127
citation_firstpage	111616
citation_doi	https://doi.org/10.1016/j.cellsig.2025.111616
citation_public_url	https://hdl.handle.net/11094/100573

AP2A1 modulates cell states between senescence and rejuvenation

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