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Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules

Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. Microtubule–actin crosstalk is poorly understood and largely regarded as the capture and regulation of microtubules by actin. Septins are filamentous guanosin...

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Autores principales: Nakos, Konstantinos, Alam, Md Noor A., Radler, Megan R., Kesisova, Ilona A., Yang, Changsong, Okletey, Joshua, Tomasso, Meagan R., Padrick, Shae B., Svitkina, Tatyana M., Spiliotis, Elias T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897426/
https://www.ncbi.nlm.nih.gov/pubmed/36475946
http://dx.doi.org/10.1073/pnas.2202803119
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author Nakos, Konstantinos
Alam, Md Noor A.
Radler, Megan R.
Kesisova, Ilona A.
Yang, Changsong
Okletey, Joshua
Tomasso, Meagan R.
Padrick, Shae B.
Svitkina, Tatyana M.
Spiliotis, Elias T.
author_facet Nakos, Konstantinos
Alam, Md Noor A.
Radler, Megan R.
Kesisova, Ilona A.
Yang, Changsong
Okletey, Joshua
Tomasso, Meagan R.
Padrick, Shae B.
Svitkina, Tatyana M.
Spiliotis, Elias T.
author_sort Nakos, Konstantinos
collection PubMed
description Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. Microtubule–actin crosstalk is poorly understood and largely regarded as the capture and regulation of microtubules by actin. Septins are filamentous guanosine-5'-triphosphate (GTP) binding proteins, which comprise the fourth component of the cytoskeleton along microtubules, actin, and intermediate filaments. Here, we report that septins mediate microtubule–actin crosstalk by coupling actin polymerization to microtubule lattices. Superresolution and platinum replica electron microscopy (PREM) show that septins localize to overlapping microtubules and actin filaments in the growth cones of neurons and non-neuronal cells. We demonstrate that recombinant septin complexes directly crosslink microtubules and actin filaments into hybrid bundles. In vitro reconstitution assays reveal that microtubule-bound septins capture and align stable actin filaments with microtubules. Strikingly, septins enable the capture and polymerization of growing actin filaments on microtubule lattices. In neuronal growth cones, septins are required for the maintenance of the peripheral actin network that fans out from microtubules. These findings show that septins directly mediate microtubule interactions with actin filaments, and reveal a mechanism of microtubule-templated actin growth with broader significance for the self-organization of the cytoskeleton and cellular morphogenesis.
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spelling pubmed-98974262023-06-07 Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules Nakos, Konstantinos Alam, Md Noor A. Radler, Megan R. Kesisova, Ilona A. Yang, Changsong Okletey, Joshua Tomasso, Meagan R. Padrick, Shae B. Svitkina, Tatyana M. Spiliotis, Elias T. Proc Natl Acad Sci U S A Biological Sciences Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. Microtubule–actin crosstalk is poorly understood and largely regarded as the capture and regulation of microtubules by actin. Septins are filamentous guanosine-5'-triphosphate (GTP) binding proteins, which comprise the fourth component of the cytoskeleton along microtubules, actin, and intermediate filaments. Here, we report that septins mediate microtubule–actin crosstalk by coupling actin polymerization to microtubule lattices. Superresolution and platinum replica electron microscopy (PREM) show that septins localize to overlapping microtubules and actin filaments in the growth cones of neurons and non-neuronal cells. We demonstrate that recombinant septin complexes directly crosslink microtubules and actin filaments into hybrid bundles. In vitro reconstitution assays reveal that microtubule-bound septins capture and align stable actin filaments with microtubules. Strikingly, septins enable the capture and polymerization of growing actin filaments on microtubule lattices. In neuronal growth cones, septins are required for the maintenance of the peripheral actin network that fans out from microtubules. These findings show that septins directly mediate microtubule interactions with actin filaments, and reveal a mechanism of microtubule-templated actin growth with broader significance for the self-organization of the cytoskeleton and cellular morphogenesis. National Academy of Sciences 2022-12-07 2022-12-13 /pmc/articles/PMC9897426/ /pubmed/36475946 http://dx.doi.org/10.1073/pnas.2202803119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Nakos, Konstantinos
Alam, Md Noor A.
Radler, Megan R.
Kesisova, Ilona A.
Yang, Changsong
Okletey, Joshua
Tomasso, Meagan R.
Padrick, Shae B.
Svitkina, Tatyana M.
Spiliotis, Elias T.
Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title_full Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title_fullStr Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title_full_unstemmed Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title_short Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
title_sort septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897426/
https://www.ncbi.nlm.nih.gov/pubmed/36475946
http://dx.doi.org/10.1073/pnas.2202803119
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