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  Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity.

Winter, J. F., Höpfner, S., Korn, K., Farnung, B., Bradshaw, C. R., Marsico, G., et al. (2012). Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity. Nature Cell Biology, 14(7), 666-676.

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 Creators:
Winter, Julia Franziska1, Author           
Höpfner, Sebastian2, Author           
Korn, Kerstin1, Author           
Farnung, Benjamin1, Author           
Bradshaw, Charles R.1, Author           
Marsico, Giovanni1, Author           
Volkmer, Michael1, Author           
Habermann, Bianca1, Author           
Zerial, Marino1, Author           
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              
2External Organizations, ou_persistent22              

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 Abstract: Apically enriched Rab11-positive recycling endosomes (Rab11-REs) are important for establishing and maintaining epithelial polarity. Yet, little is known about the molecules controlling trafficking of Rab11-REs in an epithelium in vivo. Here, we report a genome-wide, image-based RNA interference screen for regulators of Rab11-RE positioning and transport of an apical membrane protein (PEPT-1) in C. elegans intestine. Among the 356 screen hits was the 14-3-3 and partitioning defective protein PAR-5, which we found to be specifically required for Rab11-RE positioning and apicobasal polarity maintenance. Depletion of PAR-5 induced abnormal clustering of Rab11-REs to ectopic sites at the basolateral cortex containing F-actin and other apical domain components. This phenotype required key regulators of F-actin dynamics and polarity, such as Rho GTPases (RHO-1 and the Rac1 orthologue CED-10) and apical PAR proteins. Our data suggest that PAR-5 acts as a regulatory hub for a polarity-maintaining network required for apicobasal asymmetry of F-actin and proper Rab11-RE positioning.

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 Dates: 2012
 Publication Status: Issued
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 Identifiers: eDoc: 645289
Other: 4888
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Title: Nature Cell Biology
Source Genre: Journal
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Pages: - Volume / Issue: 14 (7) Sequence Number: - Start / End Page: 666 - 676 Identifier: -