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  aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division.

Galli, M., Muñoz, J., Portegijs, V., Boxem, M., Grill, S. W., Heck, A. J. R., et al. (2011). aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division. Nature Cell Biology, 13(9), 1132-1138.

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 Creators:
Galli, Matilde1, Author
Muñoz, Javier, Author
Portegijs, Vincent, Author
Boxem, Mike1, Author
Grill, Stephan W.2, Author           
Heck, Albert J R, Author
Heuvel, Sander van den1, Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: The position of the mitotic spindle controls the plane of cell cleavage and determines whether polarized cells divide symmetrically or asymmetrically. In animals, an evolutionarily conserved pathway of LIN-5 (homologues: Mud and NuMA), GPR-1/2 (homologues: Pins, LGN, AGS-3) and Gα mediates spindle positioning, and acts downstream of the conserved PAR-3-PAR-6-aPKC polarity complex. However, molecular interactions between polarity proteins and LIN-5-GPR-Gα remain to be identified. Here we describe a quantitative mass spectrometry approach for in vivo identification of protein kinase substrates. Applying this strategy to Caenorhabditis elegans embryos, we found that depletion of the polarity kinase PKC-3 results in markedly decreased levels of phosphorylation of a cluster of four LIN-5 serine residues. These residues are directly phosphorylated by PKC-3 in vitro. Phospho-LIN-5 co-localizes with PKC-3 at the anterior cell cortex and temporally coincides with a switch from anterior- to posterior-directed spindle movements in the one-cell embryo. LIN-5 mutations that prevent phosphorylation increase the extent of anterior-directed spindle movements, whereas phosphomimetic mutations decrease spindle migration. Our results indicate that anterior-located PKC-3 inhibits cortical microtubule pulling forces through direct phosphorylation of LIN-5. This molecular interaction between polarity and spindle-positioning proteins may be used broadly in cell cleavage plane determination.

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 Dates: 2011
 Publication Status: Issued
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 Identifiers: eDoc: 585169
Other: 4509
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Title: Nature Cell Biology
Source Genre: Journal
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Pages: - Volume / Issue: 13 (9) Sequence Number: - Start / End Page: 1132 - 1138 Identifier: -