From Planar Cell Polarity to Ciliogenesis and Back: The Curious Tale of the PPE and CPLANE proteins

Abstract

Why some genes are more popular than others remains an open question, but one example of this phenomenon involves the genes controlling planar cell polarity (PCP), the polarization of cells within a plane of a tissue. Indeed, the so-called 'core' PCP genes such as dishevelled, frizzled, and prickle have been extensively studied both in animal models and by human genetics. By contrast, other genes that influence PCP signaling have received far less attention. Among the latter are inturned, fuzzy, and fritz, but recent work should bring these once obscure regulators into the limelight. We provide here a brief history of planar polarity effector (PPE) and CPLANE (ciliogenesis and planar polarity effector) proteins, discuss recent advances in understanding their molecular mechanisms of action, and describe their roles in human disease.

Figure 1

A. Planar cell polarity in the Drosophila wing. Wild type wing cells extend a single distally-directed actin-based hair under the control of asymmetrically localized PCP/PPE proteins (see colors). Mutation of core PCP genes disrupts both polarity of wing hairs and PCP/PPE protein localization. Mutation of PPE genes leads to disrupted polarity as well as multiple wing hairs, but core PCP protein localization is unaffected. Mutation of Mwh disrupts polarity and elicits multiple wing hairs, while core PCP and PPE protein localization is unaffected. B. The PPE proteins act via Mwh to restrict actin assembly to the distal vertex of wing cells.

Figure 2

A. CPLANE proteins control multiple steps of ciliogenesis, acting with Daam1 and RhoA to control actin-dependent apical migration and docking of basal bodies and also recruitment of IFT-A proteins to the base of cilia. The protein structures show here are based on computational modeling reported in [51]; the interaction interfaces in the assemblage depicted are speculative,. B. Both Drosophila PPE proteins and vertebrate CPLANE proteins reciprocally interact in biochemical and proteomic assays. CPLANE proteins also interact with Jbts17 and Rsg1, proteins which appear not be encoded in the Drosophila genome. PPE proteins interact with the formin-related protein Mwh, CPLANE proteins act via the formin Daam1 and the GTPAse RhoA