In the one-celled C. elegans embryo, a complex of PAR-3 and PAR-6, two PDZ-domain-containing proteins, together with atypical protein kinase C PKC-3 are found at the anterior.
Epithelial cell polarity is maintained through the combined action of three major regulatory complexes: Crumbs complex, Par complex and Scribbled complex [ 95- 97].
Besides aPKC, the Par complex consists of Par-3 (Bazooka in flies) and Par-6.
Considering the complex role of PAR-1 in infection, related to the capacity of multiple proteases to activate PAR-1 resulting in differential cellular effects and the multiple cell types expressing PAR-1, this receptor at this moment does not represent a straightforward therapeutic target in severe pneumonia and sepsis.
To make things more complex, activation of PAR-1 by low doses of thrombin can (like APC) result in a barrier protective effect [ 8], whereas a very recent investigation provided evidence that activated coagulation factor VII (FVIIa) can exert a barrier protective effect in endothelial cells via activation of PAR-1 [ 21].
PAR-6, PAR-3, and PKC-3 constitute the anterior PAR complex, while PAR-2 localizes to the posterior cortex by the exclusion of PAR-3 [2].
In epithelial cells, Cdc42 determines the localization of Par complex to the tight junctions through interaction with Par6 and activation of aPKC (Goldstein and Macara, 2007; Joberty et al., 2000; Lin et al., 2000).
It has been shown that recruitment of Par complex and localized activation of aPKC at the nascent axon is instrumental in breaking the symmetry and enhancing the axon growth (Arimura and Kaibuchi, 2007; Shi et al., 2003).
We did not observe a synergistic effect between deletion of the Crumbs family and inactivation of the PAR complex component PAR-6, or the CCC component HMR-1.
This example is provided to indicate how complex and convoluted the interactions of PAR signalling can be and to alert the reader to the very rapid events that can accompany PAR signalling so as to affect multiple effector pathways simultaneously, even at the level of ion channel regulation.
This process also recruits the partitioning defective (PAR) complex of polarity proteins (PAR3/PAR6/PKCζ), which influence axon specification and growth.
