Reich, JD;
Hubatsch, L;
Illukkumbura, R;
Peglion, F;
Bland, T;
Hirani, N;
Goehring, NW;
(2019)
Regulated Activation of the PAR Polarity Network Ensures a Timely and Specific Response to Spatial Cues.
Current Biology
, 29
(12)
1911-1923.e5.
10.1016/j.cub.2019.04.058.
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Abstract
How do cells polarize at the correct time and in response to the correct cues? In the C. elegans zygote, the timing and geometry of polarization rely on a single dominant cue-the sperm centrosome-that matures at the end of meiosis and specifies the nascent posterior. Polarization requires that the conserved PAR proteins, which specify polarity in the zygote, be poised to respond to the centrosome. Yet, how and when PAR proteins achieve this unpolarized, but responsive, state is unknown. We show that oocyte maturation initiates a fertilization-independent PAR activation program. PAR proteins are initially not competent to polarize but gradually acquire this ability following oocyte maturation. Surprisingly, this program allows symmetry breaking even in unfertilized oocytes lacking centrosomes. Thus, if PAR proteins can respond to multiple polarizing cues, how is specificity for the centrosome achieved? Specificity is enforced by Polo-like and Aurora kinases (PLK-1 and AIR-1 in C. elegans), which impose a delay in the activation of the PAR network so that it coincides with maturation of the centrosome cue. This delay suppresses polarization by non-centrosomal cues, which can otherwise trigger premature polarization and multiple or reversed polarity domains. Taken together, these findings identify a regulatory program that enforces proper polarization by synchronizing PAR network activation with cell cycle progression, thereby ensuring that PAR proteins respond specifically to the correct cue. Temporal control of polarity network activity is likely to be a common strategy to ensure robust, dynamic, and specific polarization in response to developmentally deployed cues.
| Type: | Article |
|---|---|
| Title: | Regulated Activation of the PAR Polarity Network Ensures a Timely and Specific Response to Spatial Cues |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cub.2019.04.058 |
| Publisher version: | https://doi.org/10.1016/j.cub.2019.04.058 |
| Language: | English |
| Additional information: | © 2019 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creative commons.org/licenses/by/4.0/). |
| Keywords: | Aurora kinase, Caenorhabditis elegans, PAR proteins, Polo kinase, cell cycle, cell polarity, development, symmetry breaking, zygote |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10075568 |
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