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A High-throughput, High-content, Liquid-based C. elegans Pathosystem
Published on: July 1, 2018
PAR-6 levels are regulated by NOS-3 in a CUL-2 dependent manner in Caenorhabditiselegans
A Pacquelet1, E Zanin, C Ashiono
1ETH Zurich, Institute of Biochemistry, Schafmattstrasse 18, 8093 Zurich, Switzerland.
Abstract:
The PAR proteins have an essential and conserved function in establishing polarity in many cell types and organisms. However, their key upstream regulators remain to be identified. In C. elegans, regulators of the PAR proteins can be identified by their ability to suppress the lethality of par-2 mutant embryos. Here we show that a nos-3 loss of function mutant suppresses the lethality of par-2 mutants by regulating PAR-6 protein levels. The suppression requires the activity of the sex determination genes fem-1/2/3 and of the cullin cul-2. FEM-1 is a substrate-specific adaptor for a CUL-2-based ubiquitin ligase (CBC(FEM-1)). Interestingly, we find that CUL-2 is required for the regulation of PAR-6 levels and that PAR-6 physically interacts with FEM-1. Our data strongly suggest that PAR-6 levels are regulated by the CBC(FEM-1) ubiquitin ligase thereby uncovering a novel role for the FEM proteins and cullin-dependent degradation in regulating PAR proteins and polarity processes.
Insights
Researchers identified novel regulators of PAR proteins, crucial for cell polarity. A nos-3 mutation suppresses lethality in par-2 mutants by controlling PAR-6 protein levels via a FEM-1/CUL-2 ubiquitin ligase complex.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Partitioning defective (PAR) proteins are essential for establishing cell polarity in diverse organisms.
- Identifying upstream regulators of PAR proteins is critical for understanding polarity establishment.
- In Caenorhabditis elegans, genetic screens for suppressors of par-2 lethality identify PAR protein regulators.
Purpose of the Study:
- To identify novel regulators of PAR proteins in C. elegans.
- To elucidate the mechanism by which nos-3 regulates PAR protein levels and suppresses par-2 lethality.
- To uncover the role of FEM proteins and cullin-dependent degradation in polarity establishment.
Main Methods:
- Genetic screening in C. elegans to identify suppressors of par-2 mutant lethality.
- Analysis of PAR-6 protein levels in nos-3 loss-of-function mutants.
- Investigating the requirement of sex determination genes (fem-1/2/3) and CUL-2 in the suppression.
- Biochemical assays to determine the interaction between PAR-6 and FEM-1 and the role of CBC(FEM-1) ubiquitin ligase.
Main Results:
- A nos-3 loss-of-function mutation suppresses the lethality of par-2 mutant embryos.
- The suppression is dependent on the activity of sex determination genes fem-1/2/3 and the cullin CUL-2.
- FEM-1 acts as a substrate-specific adaptor for a CUL-2-based ubiquitin ligase (CBC(FEM-1)).
- CUL-2 is essential for regulating PAR-6 protein levels, and PAR-6 physically interacts with FEM-1.
Conclusions:
- PAR-6 protein levels are regulated by the CBC(FEM-1) ubiquitin ligase.
- This study reveals a novel mechanism for regulating PAR proteins and polarity through cullin-dependent degradation.
- The FEM proteins play a previously unrecognized role in controlling cell polarity via protein degradation pathways.
