Function of the Spectrin skeleton in regulating cell shape, cell mechanics, and epithelium architecture: a quantitative, biophysical study

Isabel M Palacios (primary)
Biochemistry, SBCS
QMUL
Guillaume Charras (secondary)
Cell and Developmental Biology
UCL

Abstract

Spectrins are conserved in all eukaryotes and in erythrocytes they crosslink actin to membrane, forming a mechanically deformable skeleton that lies directly below the plasma membrane. Although spectrins have been studied in erythrocytes, little is known about their function in other cell types. This project aims to quantitatively understand the spectrin skeleton function in regulating cell mechanics and epithelium architecture, both in vertebrates and invertebrates. This will be achieved by analysing the function of spectrins in mammalian blebbing cells and in the Drosophila follicular epithelium (FE), combining genetics, live imaging, automated image analysis, and biophysical techniques to measure cellular forces and membrane tension. These approaches will determine how spectrins dynamically regulate cell- and tissue-scale mechanics. In Drosophila, we recently found that spectrins are key to maintaining a mono-layered FE, as spectrin mutant cells form a “tumour-like” mass. We have found that perturbation of actomyosin in the submembranous cortex modulates this “tumour-like” phenotype, indicating crosstalk between these two networks. Our hypothesis suggests that the spectrins are essential to organise cortical contraction at the right levels and places, and that this maybe important for cancer


References

1. Ng BF, Selvaraj GK, Santa-Cruz Mateos C, Grosheva I, Alvarez-Garcia I, Martín-Bermudo MD and Palacios IM (2016). Alpha-Spectrin and Integrins act together to regulate actomyosin and columnarization, and to maintain a mono-layered follicular epithelium. Development. Apr 15;143(8): 1388
2. Drechsler M, Giavazzi F, Cerbino R and Palacios IM. (2017). Active diffusion and advection in the Drosophila ooplasm are due to the interplay of the microtubule and actin cytoskeletons. bioRxiv (doi: https://doi.org/10.1101/098590) and at Nature Communications, DOI : 10.1038/s41467-017-01414-6
3. Charras GT, Hu CK, Coughlin M, Mitchison TJ. Reassembly of a contractile actin cortex in cell blebs. J Cell Biol. 2006 Nov 6;175(3):477-90.
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BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyDevelopment
Techniques & Approaches
BiophysicsGeneticsImage ProcessingMicroscopy / Electrophysiology