Widely conserved signaling pathways in the establishment of cell polarity

Abstract

How are the asymmetric distributions of proteins, lipids, and RNAs established and maintained in various cell types? Studies from diverse organisms show that Par proteins, GTPases, kinases, and phosphoinositides participate in conserved signaling pathways to establish and maintain cell polarity.

Figure 1.

An overview of Par complex signaling, showing inputs (bottom) and outputs (top) with cellular functions that are targeted by these pathways (italics).

Figure 2.

Mechanisms for the transport, cortical association, and anchoring of Par3 in mammalian cells. It is not yet known if all of these mechanisms operate in any one cell type, and additional processes, such as RNA localization, might conceivably play roles in certain circumstances. Junctional adhesion molecule (JAM) is shown as an example of a transmembrane protein to which Par-3 can be anchored, but others undoubtedly exist, such as the neurotrophin receptor, p75NTR, in mammalian Schwann cells (Chan et al. 2006).

Figure 3.

A model for the interactions of the Par complex with other polarity proteins and protein kinases. This model synthesizes data from a number of laboratories, and attempts to reconcile observations that aPKC can bind directly to Par-3, but also can bind indirectly through Par-6. The direct association is inhibited by phosphorylation; whereas the indirect association is inhibited by competition for Par-6 by the Crumbs/Pals1 complex and by the Lgl polarity protein. In addition, the schematic shows Par-3 functioning to recruit other targets for aPKC, such as Numb, and the regulation of Par-6 by the Cdc42 GTPase and the Aurora A kinase.