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

The CRB polarity complex plays a major role in establishment, regulation, and maintenance of apical polarity in epithelial cells (Tepass, 1996; Roh et al., 2003; Shin et al., 2006). CRB3, ubiquitously expressed in epithelial cells, docks the CRB complex at the apical domain of the plasma membrane where it is specifically anchored (Makarova et al., 2003). PALS1 PDZ domain binds to CRB3 carboxy-terminal PDZ domain-binding motif (PBM), which consists of four terminal amino acids, E-R-L-I (Roh et al., 2002; Hurd et al., 2003; Roh et al., 2003). In MDCKII cells, knockdown of PALS1 expression by small interfering RNA leads to concurrent loss of expression of PATJ, decrease of transepithelial electrical resistance (TER), and disruption of cell polarity, as illustrated by formation of cysts with multiple lumens when MDCKII are grown in a collagen gel matrix (Straight et al., 2004). Wang and coworkers have further demonstrated that depletion of PALS1 in MDCKII cells alters the intracellular trafficking of E-cadherin, which is retained as intracellular puncta at the cell periphery and is not effectively delivered to the cell surface. As a result, both TJ and adherens junction (AJ) formation are disrupted (Wang et al., 2007). In summary, PALS1 functionally regulates and maintains the integrity of TJ and AJ, and as a consequence cell polarity in epithelial cells.