January 2019: Links between polarity protein localization, membrane trafficking and the cytoskeleton

Cellular polarity is an essential characteristic of the development and functioning of an organism. It allows the subdivision of the cell into different functional domains, both at the level of the plasma membrane and the cytoplasm, ensuring asymmetry in the functions of the cell. Establishment and maintenance of cell polarity are under the control of two main well preserved protein modules among metazoans, including PAR1 and PAR3, respectively.

By using the Drosophila oocyte as a model system, researchers from the "Polarity and Morphogenesis" team of the Jacques Monod Institute, in an article published in the eLife journal, were able to highlight a new mode of localization of the PAR3 protein coupled to membrane trafficking and microtubule-associated transport.
In the Drosophila oocyte, PAR3, at the anterior pole, and PAR1, at the posterior pole, specify the polarity axes of the future embryo by controlling the asymmetric transport of crucial determinants for development. Par3 and PAR1 are mutually exclusive by direct or indirect phosphorylations, but the fate once phosphorylated of these two cytoplasmic proteins is poorly understood.
The researchers identified several distinct and complementary mechanisms responsible for the posterior exclusion of PAR3 and its subsequent accumulation. The exclusion of PAR3 from the plasma membrane is dependent on PAR1 protein kinase and an endocytic process based on GTPase RAB5 and phosphoinositide PI (4,5) P2. In a second phase, the polarized transport of PAR3 towards the anterior cortex is carried out thanks to dynein and microtubules. This second phase again involves vesicular trafficking but this time GTPase RAB11 and recycling endosomes.
All these results suggest that the maintenance of PAR3 asymmetry is based on cooperation between membrane trafficking and dependent dynein transport. Future work will determine exactly how PAR3, a cytoplasmic protein, is connected to the endocytosis machinery and whether it is a general mechanism that can also occur in other polarized cells and in other organisms.

Contact : Sandra Claret, Antoine Guichet, team : "Polarity and Morphogenesis".

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