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

Author

Listed:
  • Maria Fankhaenel

    (University of Southampton
    University of Southampton)

  • Farahnaz S. Golestan Hashemi

    (University of Southampton
    University of Southampton)

  • Larissa Mourao

    (VIB-KULeuven Center for Cancer Biology, Herestraat 49)

  • Emily Lucas

    (University of Southampton
    University of Southampton)

  • Manal M. Hosawi

    (University of Southampton
    University of Southampton)

  • Paul Skipp

    (University of Southampton
    University of Southampton
    University of Southampton)

  • Xavier Morin

    (PSL Research University)

  • Colinda L.G.J. Scheele

    (VIB-KULeuven Center for Cancer Biology, Herestraat 49)

  • Salah Elias

    (University of Southampton
    University of Southampton)

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.

Suggested Citation

  • Maria Fankhaenel & Farahnaz S. Golestan Hashemi & Larissa Mourao & Emily Lucas & Manal M. Hosawi & Paul Skipp & Xavier Morin & Colinda L.G.J. Scheele & Salah Elias, 2023. "Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35881-x
    DOI: 10.1038/s41467-023-35881-x
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    References listed on IDEAS

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    1. Shigeru Matsumura & Mayumi Hamasaki & Takuya Yamamoto & Miki Ebisuya & Mizuho Sato & Eisuke Nishida & Fumiko Toyoshima, 2012. "ABL1 regulates spindle orientation in adherent cells and mammalian skin," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    2. Jennifer M. Rosenbluth & Ron C. J. Schackmann & G. Kenneth Gray & Laura M. Selfors & Carman Man-Chung Li & Mackenzie Boedicker & Hendrik J. Kuiken & Andrea Richardson & Jane Brock & Judy Garber & Debo, 2020. "Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Sofia Duarte & Álvaro Viedma-Poyatos & Elena Navarro-Carrasco & Alma E. Martínez & María A. Pajares & Dolores Pérez-Sala, 2019. "Vimentin filaments interact with the actin cortex in mitosis allowing normal cell division," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    4. Laura Pirovano & Simone Culurgioni & Manuel Carminati & Andrea Alfieri & Silvia Monzani & Valentina Cecatiello & Chiara Gaddoni & Francesca Rizzelli & James Foadi & Sebastiano Pasqualato & Marina Mape, 2019. "Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    5. Scott E. Williams & Slobodan Beronja & H. Amalia Pasolli & Elaine Fuchs, 2011. "Asymmetric cell divisions promote Notch-dependent epidermal differentiation," Nature, Nature, vol. 470(7334), pages 353-358, February.
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    Cited by:

    1. Volker Gerke & Felicity N. E. Gavins & Michael Geisow & Thomas Grewal & Jyoti K. Jaiswal & Jesper Nylandsted & Ursula Rescher, 2024. "Annexins—a family of proteins with distinctive tastes for cell signaling and membrane dynamics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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