Different domains of C. elegans PAR-3 are required at different times in development

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Developmental Biology (Impact Factor: 3.55). 08/2010; 344(2):745-57. DOI: 10.1016/j.ydbio.2010.05.506
Source: PubMed


Polarity is a fundamental cellular feature that is critical for generating cell diversity and maintaining organ functions during development. In C. elegans, the one-cell embryo is polarized via asymmetric localization of the PAR proteins, which in turn are required to establish the future anterior-posterior axis of the embryo. PAR-3, a conserved PDZ domain-containing protein, acts with PAR-6 and PKC-3 (atypical protein kinase; aPKC) to regulate cell polarity and junction formation in a variety of cell types. To understand how PAR-3 localizes and functions during C. elegans development, we produced targeted mutations and deletions of conserved domains of PAR-3 and examined the localization and function of the GFP-tagged proteins in C. elegans embryos and larvae. We find that CR1, the PAR-3 self-oligomerization domain, is required for PAR-3 cortical distribution and function only during early embryogenesis and that PDZ2 is required for PAR-3 to accumulate stably at the cell periphery in early embryos and at the apical surface in pharyngeal and intestinal epithelial cells. We also show that phosphorylation at S863 by PKC-3 is not essential in early embryogenesis, but is important in later development. Surprisingly neither PDZ1 nor PDZ3 are essential for localization or function. Our results indicate that the different domains and phosphorylated forms of PAR-3 can have different roles during C. elegans development.

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    • "The following strains were used: TH120 (PAR-2-GFP; mCherry-PAR-6) [Schonegg et al., 2007] MAD3 (DYN- 1-GFP) [Nakayama et al., 2009], KK653 (unc- 32(e189)par-3(it71)/qC1 III) [Li et al., 2010] and N2 (Wild type) [Brenner, 1974]. Worms were maintained and cultured at 25 C as described by Brenner [1974]. "
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    ABSTRACT: PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time. © 2012 Wiley Periodicals, Inc.
    Cytoskeleton 10/2012; 69(10):826-39. DOI:10.1002/cm.21053 · 3.12 Impact Factor
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    • "within PAR-3 is not required for PAR-3 function (Li et al., 2010a), this mechanism alone cannot explain the cortical exclusion of PAR- 3 by PAR-2. In addition, it is not known if and how PAR-2 regulates PAR-1. "
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    ABSTRACT: Cell polarity is essential for cells to divide asymmetrically, form spatially restricted subcellular structures and participate in three-dimensional multicellular organization. PAR proteins are conserved polarity regulators that function by generating cortical landmarks that establish dynamic asymmetries in the distribution of effector proteins. Here, we review recent findings on the role of PAR proteins in cell polarity in C. elegans and Drosophila, and emphasize the links that exist between PAR networks and cytoskeletal proteins that both regulate PAR protein localization and act as downstream effectors to elaborate polarity within the cell.
    Development 03/2011; 138(5):799-809. DOI:10.1242/dev.053538 · 6.46 Impact Factor
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