Cilia, Wnt signaling, and the cytoskeleton

Matthew W Kelley,Helen L May-Simera

doi:10.1186/2046-2530-1-7

Abstract

Primary cilia have recently been highlighted as key regulators in development and disease. This review focuses on current work demonstrating the broad role of cilia-related proteins in developmental signaling systems. Of particular consideration is the importance of the basal body region, located at the base of the cilium, in its role as a focal point for many signaling pathways and as a microtubule organizing center. As the cilium is effectively a microtubular extension of the cytoskeleton, investigating connections between the cilium and the cytoskeleton provides greater insight into signaling and cell function. Of the many signaling pathways associated with primary cilia, the most extensively studied in association with the cytoskeleton and cytoskeletal rearrangements are both canonical and non-canonical Wnt pathways. One of the key concepts currently emerging is a possible additional role for the traditionally 'cilia-related' proteins in other aspects of cellular processes. In many cases, disruption of such processes manifests at the level of the cilium. While the involvement of cilia and cilia-related proteins in signaling pathways is currently being unraveled, there is a growing body of evidence to support the notion that ciliary proteins are required not only for regulation of Wnt signaling, but also as downstream effectors of Wnt signaling. This review summarizes recent advances in our understanding of the involvement of cilia and basal body proteins in Wnt signaling pathways.

Highlights

The primary cilium had long been ignored by biologists and was considered to be a vestigial remnant of evolution, similar to the human appendix
Cilia were classified as either motile or primary cilia based on their internal structure
A recent proteomic screen found several planar cell polarity (PCP)-associated proteins in the human centrosome such as PRICKLE3, SCRIB, CCDC66, and Albatross [104]. This screen identified asymmetrically localizing centriolar proteins and differentially aged centrioles in cell division (Figure 2), which appear to be important in cell polarization and stem cell fate determination via asynchronous microtubule spindle orientation and primary cilia growth [39,104]

Summary

Introduction

The primary cilium had long been ignored by biologists and was considered to be a vestigial remnant of evolution, similar to the human appendix. A recent proteomic screen found several PCP-associated proteins in the human centrosome such as PRICKLE3, SCRIB, CCDC66, and Albatross [104] This screen identified asymmetrically localizing centriolar proteins and differentially aged centrioles in cell division (Figure 2), which appear to be important in cell polarization and stem cell fate determination via asynchronous microtubule spindle orientation and primary cilia growth [39,104]. In regard to ciliogenesis, APC has been shown to be one of the few proteins that localizes asymmetrically to mother vs daughter centrioles and may play a role in primary cilia formation and function [104] This most likely occurs via regulation of actin or microtubules at the basal body region. The basal body, an emerging signaling ‘hotspot’ perfectly located at the base of the ‘sensory-loaded’ cilium might be an ideal cellular location for the switch

Conclusions

Nigg EA

15. Scholey JM

31. Sorokin S

77. McNeill H