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The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling

BACKGROUND: The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are invo...

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Autores principales: Wang, Yinna, Liao, Guoning, Wu, Yidi, Wang, Ruping, Tang, Dale D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268400/
https://www.ncbi.nlm.nih.gov/pubmed/37316833
http://dx.doi.org/10.1186/s12931-023-02473-8
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author Wang, Yinna
Liao, Guoning
Wu, Yidi
Wang, Ruping
Tang, Dale D.
author_facet Wang, Yinna
Liao, Guoning
Wu, Yidi
Wang, Ruping
Tang, Dale D.
author_sort Wang, Yinna
collection PubMed
description BACKGROUND: The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are involved in smooth muscle contraction. Regulation of complex cytoskeletal signaling is not entirely elucidated. The aim of this study was to evaluate the role of nestin (a type VI intermediate filament protein) in cytoskeletal signaling in airway smooth muscle. METHODS: Nestin expression in human airway smooth muscle (HASM) was knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain (MLC) phosphorylation, and contraction were evaluated by cellular and physiological approaches. Moreover, we assessed the effects of non-phosphorylatable nestin mutant on these biological processes. RESULTS: Nestin KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Moreover, contractile stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD diminished nestin phosphorylation at this residue. CONCLUSIONS: Nestin is an essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in smooth muscle. Plk1 and nestin form an activation loop during contractile stimulation.
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spelling pubmed-102684002023-06-15 The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling Wang, Yinna Liao, Guoning Wu, Yidi Wang, Ruping Tang, Dale D. Respir Res Research BACKGROUND: The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are involved in smooth muscle contraction. Regulation of complex cytoskeletal signaling is not entirely elucidated. The aim of this study was to evaluate the role of nestin (a type VI intermediate filament protein) in cytoskeletal signaling in airway smooth muscle. METHODS: Nestin expression in human airway smooth muscle (HASM) was knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain (MLC) phosphorylation, and contraction were evaluated by cellular and physiological approaches. Moreover, we assessed the effects of non-phosphorylatable nestin mutant on these biological processes. RESULTS: Nestin KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Moreover, contractile stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD diminished nestin phosphorylation at this residue. CONCLUSIONS: Nestin is an essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in smooth muscle. Plk1 and nestin form an activation loop during contractile stimulation. BioMed Central 2023-06-14 2023 /pmc/articles/PMC10268400/ /pubmed/37316833 http://dx.doi.org/10.1186/s12931-023-02473-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Yinna
Liao, Guoning
Wu, Yidi
Wang, Ruping
Tang, Dale D.
The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title_full The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title_fullStr The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title_full_unstemmed The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title_short The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
title_sort intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268400/
https://www.ncbi.nlm.nih.gov/pubmed/37316833
http://dx.doi.org/10.1186/s12931-023-02473-8
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