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Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis

Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
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 Gαi 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 Gαi 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.

2041-1723
Fankhaenel, Maria
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Hashemi, Farahnaz S Golestan
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Mourao, Larissa
59ef15a4-d496-4953-9675-c4628efa2b82
Lucas, Emily
7342612b-4010-4b96-a009-372de1dccc7a
Hosawi, Manal M
2a002947-9222-475d-b915-52bbc332ae5b
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Morin, Xavier
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Scheele, Colinda L G J
1d639d27-dba6-4fc1-b739-2f8a8b2fb938
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3
Fankhaenel, Maria
f8f09d0e-8f56-4a25-a2f0-88ed28bb1fe2
Hashemi, Farahnaz S Golestan
6dab1094-bde2-4d43-8617-3d1033763247
Mourao, Larissa
59ef15a4-d496-4953-9675-c4628efa2b82
Lucas, Emily
7342612b-4010-4b96-a009-372de1dccc7a
Hosawi, Manal M
2a002947-9222-475d-b915-52bbc332ae5b
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Morin, Xavier
5e3b7885-7217-49be-831f-2ad439acf367
Scheele, Colinda L G J
1d639d27-dba6-4fc1-b739-2f8a8b2fb938
Elias, Salah
a9b11116-8efb-44b3-8241-2f0f2af847c3

Fankhaenel, Maria, Hashemi, Farahnaz S Golestan, Mourao, Larissa, Lucas, Emily, Hosawi, Manal M, Skipp, Paul, Morin, Xavier, Scheele, Colinda L G J and Elias, Salah (2023) Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis. Nature Communications, 14 (1), [151]. (doi:10.1038/s41467-023-35881-x).

Record type: Article

Abstract

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 Gαi 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 Gαi 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.

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Accepted/In Press date: 5 January 2023
Published date: 11 January 2023
Additional Information: © 2023. Crown.

Identifiers

Local EPrints ID: 475065
URI: http://eprints.soton.ac.uk/id/eprint/475065
ISSN: 2041-1723
PURE UUID: 585d54a6-3b02-430d-9920-9d268223f5c8
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Salah Elias: ORCID iD orcid.org/0000-0003-1005-438X

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Date deposited: 09 Mar 2023 19:01
Last modified: 06 Jun 2024 01:59

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Contributors

Author: Farahnaz S Golestan Hashemi
Author: Larissa Mourao
Author: Emily Lucas
Author: Manal M Hosawi
Author: Paul Skipp ORCID iD
Author: Xavier Morin
Author: Colinda L G J Scheele
Author: Salah Elias ORCID iD

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