Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fankhaenel, Maria, Hashemi, Farahnaz S. Golestan, Mourao, Larissa, Lucas, Emily, Hosawi, Manal M., Skipp, Paul, Morin, Xavier, Scheele, Colinda L.G.J., Elias, Salah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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
_version_ 1784868455058505728
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
work_keys_str_mv AT fankhaenelmaria annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT hashemifarahnazsgolestan annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT mouraolarissa annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT lucasemily annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT hosawimanalm annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT skipppaul annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT morinxavier annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT scheelecolindalgj annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis
AT eliassalah annexina1isapolaritycuethatdirectsmitoticspindleorientationduringmammalianepithelialmorphogenesis