Interplay between the plasma membrane and cell–cell adhesion maintains epithelial identity for correct polarised cell divisions

Author:

Hosawi Manal M.12ORCID,Cheng Jiaoqi12,Fankhaenel Maria12,Przewloka Marcin R.12ORCID,Elias Salah12ORCID

Affiliation:

1. , University of Southampton 1 School of Biological Sciences , Southampton SO17 1BJ , UK

2. , University of Southampton 2 Institute for Life Sciences , Southampton SO17 1BJ , UK

Abstract

ABSTRACT Polarised epithelial cell divisions represent a fundamental mechanism for tissue maintenance and morphogenesis. Morphological and mechanical changes in the plasma membrane influence the organisation and crosstalk of microtubules and actin at the cell cortex, thereby regulating the mitotic spindle machinery and chromosome segregation. Yet, the precise mechanisms linking plasma membrane remodelling to cell polarity and cortical cytoskeleton dynamics to ensure accurate execution of mitosis in mammalian epithelial cells remain poorly understood. Here, we manipulated the density of mammary epithelial cells in culture, which led to several mitotic defects. Perturbation of cell–cell adhesion formation impairs the dynamics of the plasma membrane, affecting the shape and size of mitotic cells and resulting in defects in mitotic progression and the generation of daughter cells with aberrant architecture. In these conditions, F- actin–astral microtubule crosstalk is impaired, leading to mitotic spindle misassembly and misorientation, which in turn contributes to chromosome mis-segregation. Mechanistically, we identify S100 Ca2+-binding protein A11 (S100A11) as a key membrane-associated regulator that forms a complex with E-cadherin (CDH1) and the leucine-glycine-asparagine repeat protein LGN (also known as GPSM2) to coordinate plasma membrane remodelling with E-cadherin-mediated cell adhesion and LGN-dependent mitotic spindle machinery. Thus, plasma membrane-mediated maintenance of mammalian epithelial cell identity is crucial for correct execution of polarised cell divisions, genome maintenance and safeguarding tissue integrity.

Funder

Wellcome Trust

Medical Research Council

Ministry of Education – Kingdom of Saudi Arabia

University of Southampton

Publisher

The Company of Biologists

Subject

Cell Biology

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