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Apical transport of Crumbs maintains epithelial cell polarity

M Aguilar-Aragon, G Fletcher, View ORCID ProfileBJ Thompson
doi: https://doi.org/10.1101/592311
M Aguilar-Aragon
1The Francis Crick Institute, 1 Midland Rd, NW1 1AT, London, United Kingdom
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G Fletcher
1The Francis Crick Institute, 1 Midland Rd, NW1 1AT, London, United Kingdom
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BJ Thompson
1The Francis Crick Institute, 1 Midland Rd, NW1 1AT, London, United Kingdom
2The John Curtin School of Medical Research, The Australian National University, 131 Garran Rd, Acton, ACT 2601, Canberra, Australia
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  • ORCID record for BJ Thompson
  • For correspondence: barry.thompson@crick.ac.uk barry.thompson@anu.edu.au
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Abstract

Crumbs (Crb in Drosophila; CRB1-3 in mammals) is a transmembrane determinant of epithelial cell polarity and a regulator of Hippo signalling. Crb is normally localized to apical cell-cell contacts, just above adherens junctions, but how apical trafficking of Crb is regulated in epithelial cells remains unclear. We use the Drosophila follicular epithelium to demonstrate that polarized trafficking of Crb is mediated by transport along microtubules by the motor protein Dynein and along actin filaments by the motor protein Myosin-V (MyoV). Blocking transport of Crb-containing vesicles by Dynein or MyoV leads to accumulation of Crb within Rab11 endosomes, rather than apical delivery. The final steps of Crb delivery and stabilisation at the plasma membrane requires the exocyst complex and three apical FERM domain proteins – Merlin, Moesin and Expanded – whose simultaneous loss disrupts apical localization of Crb. Accordingly, a knock-in deletion of the Crb FERM-binding motif (FBM) also impairs apical localization. Finally, overexpression of Crb challenges this system, creating a sensitized background to identify components involved in cytoskeletal polarization, apical membrane trafficking and stabilisation of Crb at the apical domain.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 28, 2019.
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Apical transport of Crumbs maintains epithelial cell polarity
M Aguilar-Aragon, G Fletcher, BJ Thompson
bioRxiv 592311; doi: https://doi.org/10.1101/592311
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Apical transport of Crumbs maintains epithelial cell polarity
M Aguilar-Aragon, G Fletcher, BJ Thompson
bioRxiv 592311; doi: https://doi.org/10.1101/592311

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