A steady-state pool of calcium-dependent actin is maintained by Homer and controls epithelial mechanosensation.
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| Názov: | A steady-state pool of calcium-dependent actin is maintained by Homer and controls epithelial mechanosensation. |
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| Autori: | Matsuzawa K; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan., Suzuki M; Amphibian Research Center, Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8526, Japan., Cho Y; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan., Fujinaga R; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan., Ikenouchi J; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2025 Oct 28; Vol. 122 (43), pp. e2509784122. Date of Electronic Publication: 2025 Oct 24. |
| Spôsob vydávania: | Journal Article |
| Jazyk: | English |
| Informácie o časopise: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : National Academy of Sciences |
| Výrazy zo slovníka MeSH: | Calcium*/metabolism , Epithelial Cells*/metabolism , Actins*/metabolism , Mechanotransduction, Cellular*/physiology , Homer Scaffolding Proteins*/metabolism , Homer Scaffolding Proteins*/genetics, Animals ; Mice ; Calcium Signaling ; Actin Cytoskeleton/metabolism ; Humans ; Mice, Knockout ; Wound Healing ; Endoplasmic Reticulum/metabolism |
| Abstrakt: | Competing Interests: Competing interests statement:The authors declare no competing interest. Epithelial cells are inherently contractile and in homeostasis, tissue integrity is maintained by balancing the uneven contractile forces in neighboring cells at the cell-cell interface. By contrast, epithelial cells can utilize an imbalance in contractile force to communicate various information to induce tissue-wide response as in wound healing. Contractility is generated and processed at the apical junctional complex (AJC) by the dynamic behavior of the actin cytoskeleton. Calcium signaling can pattern cellular responses based on its reach and amplitude and the actin cytoskeleton is supported by its wide ranging effects on actin regulators. Calcium transients regulate various cell behaviors associated with actin remodeling, such as in damage response and developmental morphogenesis. Here, we report that calcium maintains an adaptive pool of AJC-associated actin that is sensitive to tension and encoded by calcium dynamics. For this, the recently identified epithelial polarity module Homer-MUPP1/PatJ is required. Homer regulates calcium signaling in various tissue contexts through interaction with numerous components of the endoplasmic reticulum (ER) and plasma membrane (PM) calcium signal toolkit. Knockout of either Homer or MUPP1/PatJ attenuated tension-induced calcium response and severely disrupted wound healing migration, which is dependent on guidance input through AJC tension. We also show that Homer is integral to early embryonic neurodevelopment as its suppression causes failure of neural tube closure. Our findings highlight the critical role of localized calcium dynamics on AJC actin remodeling and cellular behavior, elucidating the means of tissue coordination through intercellular tension. |
| Grant Information: | JP25H01325 MEXT | Japan Society for the Promotion of Science (JSPS); JP25H00994 MEXT | Japan Society for the Promotion of Science (JSPS); JP23KJ1689 MEXT | Japan Society for the Promotion of Science (JSPS); JP22K06225 MEXT | Japan Society for the Promotion of Science (JSPS); JPMJFR204L MEXT | JST | Fusion Oriented REsearch for disruptive Science and Technology (FOREST); no reference number Takeda Science Foundation (TSF); no reference number Toyota Physical and Chemical Research Institute (TPCRI) |
| Contributed Indexing: | Keywords: Homer; MUPP1; PatJ; actin; calcium |
| Substance Nomenclature: | SY7Q814VUP (Calcium) 0 (Actins) 0 (Homer Scaffolding Proteins) |
| Entry Date(s): | Date Created: 20251024 Date Completed: 20251024 Latest Revision: 20251105 |
| Update Code: | 20251105 |
| PubMed Central ID: | PMC12582288 |
| DOI: | 10.1073/pnas.2509784122 |
| PMID: | 41134626 |
| Databáza: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: Competing interests statement:The authors declare no competing interest.<br />Epithelial cells are inherently contractile and in homeostasis, tissue integrity is maintained by balancing the uneven contractile forces in neighboring cells at the cell-cell interface. By contrast, epithelial cells can utilize an imbalance in contractile force to communicate various information to induce tissue-wide response as in wound healing. Contractility is generated and processed at the apical junctional complex (AJC) by the dynamic behavior of the actin cytoskeleton. Calcium signaling can pattern cellular responses based on its reach and amplitude and the actin cytoskeleton is supported by its wide ranging effects on actin regulators. Calcium transients regulate various cell behaviors associated with actin remodeling, such as in damage response and developmental morphogenesis. Here, we report that calcium maintains an adaptive pool of AJC-associated actin that is sensitive to tension and encoded by calcium dynamics. For this, the recently identified epithelial polarity module Homer-MUPP1/PatJ is required. Homer regulates calcium signaling in various tissue contexts through interaction with numerous components of the endoplasmic reticulum (ER) and plasma membrane (PM) calcium signal toolkit. Knockout of either Homer or MUPP1/PatJ attenuated tension-induced calcium response and severely disrupted wound healing migration, which is dependent on guidance input through AJC tension. We also show that Homer is integral to early embryonic neurodevelopment as its suppression causes failure of neural tube closure. Our findings highlight the critical role of localized calcium dynamics on AJC actin remodeling and cellular behavior, elucidating the means of tissue coordination through intercellular tension. |
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| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.2509784122 |