PAR-6 is required for junction formation but not apicobasal polarization inC. elegansembryonic epithelial cells

Abstract

Epithelial cells perform important roles in the formation and function of organs and the genesis of many solid tumors. A distinguishing feature of epithelial cells is their apicobasal polarity and the presence of apical junctions that link cells together. The interacting proteins Par-6 (a PDZ and CRIB domain protein) and aPKC (an atypical protein kinase C) localize apically in fly and mammalian epithelial cells and are important for apicobasal polarity and junction formation. Caenorhabditis elegans PAR-6 and PKC-3/aPKC also localize apically in epithelial cells, but a role for these proteins in polarizing epithelial cells or forming junctions has not been described. Here, we use a targeted protein degradation strategy to remove both maternal and zygotic PAR-6 from C. elegans embryos before epithelial cells are born. We find that PKC-3 does not localize asymmetrically in epithelial cells lacking PAR-6, apical junctions are fragmented, and epithelial cells lose adhesion with one another. Surprisingly, junction proteins still localize apically, indicating that PAR-6 and asymmetric PKC-3 are not needed for epithelial cells to polarize. Thus, whereas the role of PAR-6 in junction formation appears to be widely conserved, PAR-6-independent mechanisms can be used to polarize epithelial cells.

Development and Cell Polarity of the C. elegans Intestine

“…In brief, these events include the correct specification and asymmetric division of the intestinal founder cell EMS (Bossinger and Schierenberg, 1996;Goldstein, 1992;Han, 1997;Kormish et al, 2010;Schierenberg, 1987;see Fig.2 for further details), the ingression of the intestinal precusor cell Ea and Ep during gastrulation ( Fig.5B-C ;Chisholm, 2006;Putzke and Rothman, 2003;Rohrschneider and Nance, 2009;Sawyer et al, 2009;Schierenberg, 2005;Schierenberg, 2006), the cytoplasmic polarization of intestinal primordial cells ( Fig.5D; Achilleos et al, 2010;Bossinger et al, 2001;Leung et al, 1999;Totong et al, 2007), the formation of apical adherens junction and the generation of the future lumen within the primordium (Fig.5E'-E''; Leung et al, 1999), the intercalation of specific sets of cells (Hoffmann et al, 2010;Leung et al, 1999), the invariant 'twist' in the anterior of the intestinal primordium (Hermann et al, 2000), and finally the differentiation of the late embryonic, larval and adult intestine that has been proposed to be under the control of the GATA-factor ELT-2 (McGhee et al, 2009;McGhee et al, 2007;Pauli et al, 2006).…”

“…The CeAJ is a belt-like junctional structure that encircles the apex of polarized epithelial cells and resembles the ZA in other systems. By immunohistochemistry, the apicolateral membrane domain can be subdivided into four subdomains (Fig.6): the PPC together with the Drosophila Crumbs homolog CRB-1 and the multi PDZ-domain containing protein MAGI-1 (Achilleos et al, 2010;Aono et al, 2004;Bossinger et al, 2001;Stetak and Hajnal, 2011;Totong et al, 2007), the catenin-cadherin complex (CCC; Costa et al, 1998;Grana et al, 2010;Kwiatkowski et al, 2010), the DLG-1-AJM-1 complex (DAC; Bossinger et al, 2001;Firestein and Rongo, 2001;Köppen et al, 2001;Lockwood et al, 2008;McMahon et al, 2001) and the LET-413 protein Legouis et al, 2000;Legouis et al, 2003;Lockwood et al, 2008;Pilipiuk et al, 2009;Segbert et al, 2004).…”

“…the CCC and DAC (Köppen et al, 2001;Kwiatkowski et al, 2010;Lockwood et al, 2008) at the future apical pole (Achilleos et al, 2010), second the assembly of a junctional belt around the apex of epithelial cells (Totong et al, 2007), third and fourth the maintenance of epithelial cell polarity Legouis et al, 2000) and cell-cell adhesion van Fürden et al, 2004).…”

“…In very elegant experiments, a targeted protein degradation strategy was used to remove both maternal and zygotic PAR-3 (par-3M/Z) from C. elegans embryos before epithelial polarization starts (Achilleos et al, 2010;Totong et al, 2007).…”

Tetraspanin KAI1/CD82 inhibits cell migration-related cellular events via reorganizing actin network

“…When a non-migrating cell encounters chemotactic molecules, its cell body will transform into two distinct portions: the "front" portion, ie., the forward moving portion, and the"back" portion, ie., the retracting rear portion localizes. Small Rho GTPases family member Cdc42 (Stowers et al, 1995;Wedlich-Soldner et al, 2003;Watanabe et al, 2004;Etienne-Manneville et al, 2005), PAR proteins (PAR3 and PAR6) (Nagai-Tamai et al, 2002;Suzuki et al, 2002;Macara, 2004;Suzuki et al, 2004;Gerard et al, 2007;Totong et al, 2007), and atypical protein kinase C (aPKC) Suzuki et al, 2004) are participating in polarization. After polarization has occurred, multiple overlapping signaling pathways from small RhoGTPases, PI3K, integrin, microtubules and vesicular transport will maintain the stability of the polarization.…”