The SARS Coronavirus E Protein Interacts with PALS1 and Alters Tight Junction Formation and Epithelial Morphogenesis

Teoh, Kim-Tat; Siu, Yu-Lam; Chan, Wing-Lim; Schlüter, Marc A.; Liu, Chia-Jen; Peiris, J. S. Malik; Bruzzone, Roberto; Margolis, Benjamin; Nal, Béatrice

Cell polarity is maintained by three protein complexes, the CRB, PAR, and SCRIB complexes, that act in concert to control the functional development of a polarized epithelium (reviewed in Shin et al., 2006; Suzuki and Ohno, 2006; Yamanaka and Ohno, 2008). The CRB complex consists of CRUMBS3 (CRB3), PALS1, and PATJ (Roh et al., 2002; Hurd et al., 2003; Roh et al., 2003). PALS1 (Protein Associated with Caenorhabditis elegans Lin-7 protein 1) belongs to the group of PDZ (Post-synaptic density protein-95/Discs Large/Zonula occludens-1) domain-containing proteins that function as scaffolds for signaling proteins and are involved in diverse cellular functions (reviewed in Schneeberger and Lynch, 2004; Miyoshi and Takai, 2005; Shin et al., 2006; Wang and Margolis, 2007). PALS1 is the central component of the CRB complex and is the ortholog of Drosophila melanogaster Stardust, key regulator of cellular polarity during embryogenesis (Kamberov et al., 2000). It is a member of the membrane-associated guanylate kinase (MAGUK) protein family and is also known as MPP5 (membrane protein, palmitoylated 5) in humans. PALS1 contains 675 amino acids organized in the following functional domains: two L27 motifs, one PDZ, one SH3 (Src Homology 3), one band 4.1, and one Guk (Guanylate kinase) domains (Kamberov et al., 2000).