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Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
Oriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved protein complex formed by the G(αi) subunit of heterotrimeric G prot...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834401/ https://www.ncbi.nlm.nih.gov/pubmed/36631478 http://dx.doi.org/10.1038/s41467-023-35881-x |
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author | Fankhaenel, Maria Hashemi, Farahnaz S. Golestan Mourao, Larissa Lucas, Emily Hosawi, Manal M. Skipp, Paul Morin, Xavier Scheele, Colinda L.G.J. Elias, Salah |
author_facet | Fankhaenel, Maria Hashemi, Farahnaz S. Golestan Mourao, Larissa Lucas, Emily Hosawi, Manal M. Skipp, Paul Morin, Xavier Scheele, Colinda L.G.J. Elias, Salah |
author_sort | Fankhaenel, Maria |
collection | PubMed |
description | Oriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved protein complex formed by the G(αi) subunit of heterotrimeric G proteins, the Leucine-Glycine-Asparagine repeat protein (LGN) and the nuclear mitotic apparatus protein. However, the polarity cues that control cortical patterning of this ternary complex remain largely unknown in mammalian epithelia. Here we identify the membrane-associated protein Annexin A1 (ANXA1) as an interactor of LGN in mammary epithelial cells. Annexin A1 acts independently of G(αi) to instruct the accumulation of LGN and nuclear mitotic apparatus protein at the lateral cortex to ensure cortical anchoring of Dynein-Dynactin and astral microtubules and thereby planar alignment of the mitotic spindle. Loss of Annexin A1 randomises mitotic spindle orientation, which in turn disrupts epithelial architecture and luminogenesis in three-dimensional cultures of primary mammary epithelial cells. Our findings establish Annexin A1 as an upstream cortical cue that regulates LGN to direct planar cell divisions during mammalian epithelial morphogenesis. |
format | Online Article Text |
id | pubmed-9834401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98344012023-01-13 Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis Fankhaenel, Maria Hashemi, Farahnaz S. Golestan Mourao, Larissa Lucas, Emily Hosawi, Manal M. Skipp, Paul Morin, Xavier Scheele, Colinda L.G.J. Elias, Salah Nat Commun Article Oriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved protein complex formed by the G(αi) subunit of heterotrimeric G proteins, the Leucine-Glycine-Asparagine repeat protein (LGN) and the nuclear mitotic apparatus protein. However, the polarity cues that control cortical patterning of this ternary complex remain largely unknown in mammalian epithelia. Here we identify the membrane-associated protein Annexin A1 (ANXA1) as an interactor of LGN in mammary epithelial cells. Annexin A1 acts independently of G(αi) to instruct the accumulation of LGN and nuclear mitotic apparatus protein at the lateral cortex to ensure cortical anchoring of Dynein-Dynactin and astral microtubules and thereby planar alignment of the mitotic spindle. Loss of Annexin A1 randomises mitotic spindle orientation, which in turn disrupts epithelial architecture and luminogenesis in three-dimensional cultures of primary mammary epithelial cells. Our findings establish Annexin A1 as an upstream cortical cue that regulates LGN to direct planar cell divisions during mammalian epithelial morphogenesis. Nature Publishing Group UK 2023-01-11 /pmc/articles/PMC9834401/ /pubmed/36631478 http://dx.doi.org/10.1038/s41467-023-35881-x Text en © Crown 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Fankhaenel, Maria Hashemi, Farahnaz S. Golestan Mourao, Larissa Lucas, Emily Hosawi, Manal M. Skipp, Paul Morin, Xavier Scheele, Colinda L.G.J. Elias, Salah Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title | Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title_full | Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title_fullStr | Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title_full_unstemmed | Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title_short | Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
title_sort | annexin a1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834401/ https://www.ncbi.nlm.nih.gov/pubmed/36631478 http://dx.doi.org/10.1038/s41467-023-35881-x |
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