The multifaceted roles of microtubule-associated proteins in the primary cilium and ciliopathies

Abstract

The primary cilium is a conserved microtubule-based organelle that is critical for transducing developmental, sensory and homeostatic signaling pathways. It comprises an axoneme with nine parallel doublet microtubules extending from the basal body, surrounded by the ciliary membrane. The axoneme exhibits remarkable stability, serving as the skeleton of the cilium in order to maintain its shape and provide tracks to ciliary trafficking complexes. Although ciliary trafficking and signaling have been exhaustively characterized over the years, less is known about the unique structural and functional complexities of the axoneme. Recent work has yielded new insights into the mechanisms by which the axoneme is built with its proper length and architecture, particularly regarding the activity of microtubule-associated proteins (MAPs). In this Review, we first summarize current knowledge about the architecture, composition and specialized compartments of the primary cilium. Next, we discuss the mechanistic underpinnings of how a functional cilium is assembled, maintained and disassembled through the regulation of its axonemal microtubules. We conclude by examining the diverse localizations and functions of ciliary MAPs for the pathobiology of ciliary diseases.