Spa2 remodels ADP-actin via molecular condensation under glucose starvation
Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structur...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/178830 |
| _version_ | 1811688334043381760 |
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| author | Ma, Qianqian Surya, Wahyu He, Danxia Yang, Hanmeng Han, Xiao Nai, Mui Hoon Lim, Chwee Teck Torres, Jaume Miao, Yansong |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ma, Qianqian Surya, Wahyu He, Danxia Yang, Hanmeng Han, Xiao Nai, Mui Hoon Lim, Chwee Teck Torres, Jaume Miao, Yansong |
| author_sort | Ma, Qianqian |
| collection | NTU |
| description | Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity. |
| first_indexed | 2024-10-01T05:30:33Z |
| format | Journal Article |
| id | ntu-10356/178830 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:30:33Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1788302024-07-08T15:32:04Z Spa2 remodels ADP-actin via molecular condensation under glucose starvation Ma, Qianqian Surya, Wahyu He, Danxia Yang, Hanmeng Han, Xiao Nai, Mui Hoon Lim, Chwee Teck Torres, Jaume Miao, Yansong School of Biological Sciences Institute for Digital Molecular Analytics and Science Medicine, Health and Life Sciences Actin binding protein Glucose Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity. Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This study was supported by MOE Tier 2 (MOE-T2EP30121-0015), National Research Foundation Singapore under its Open Fund - Individual Research Grant (MOH-000955) and administered by the Singapore Ministry of Health’s National Medical Research Council, National Research Foundation Singapore NRF-NRFI08-2022- 0012, and MOE Tier 3 (MOE2019-T3-1-012) to Y.M. in Singapore. 2024-07-08T06:34:13Z 2024-07-08T06:34:13Z 2024 Journal Article Ma, Q., Surya, W., He, D., Yang, H., Han, X., Nai, M. H., Lim, C. T., Torres, J. & Miao, Y. (2024). Spa2 remodels ADP-actin via molecular condensation under glucose starvation. Nature Communications, 15(1), 4491-. https://dx.doi.org/10.1038/s41467-024-48863-4 2041-1723 https://hdl.handle.net/10356/178830 10.1038/s41467-024-48863-4 38802374 2-s2.0-85194521557 1 15 4491 en MOE-T2EP30121-0015 MOH-000955 NRF-NRFI08-2022- 0012 MOE2019-T3-1-012 Nature Communications © 2024 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Actin binding protein Glucose Ma, Qianqian Surya, Wahyu He, Danxia Yang, Hanmeng Han, Xiao Nai, Mui Hoon Lim, Chwee Teck Torres, Jaume Miao, Yansong Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title | Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title_full | Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title_fullStr | Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title_full_unstemmed | Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title_short | Spa2 remodels ADP-actin via molecular condensation under glucose starvation |
| title_sort | spa2 remodels adp actin via molecular condensation under glucose starvation |
| topic | Medicine, Health and Life Sciences Actin binding protein Glucose |
| url | https://hdl.handle.net/10356/178830 |
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