Microtubule-associated proteins and emerging links to primary cilium structure, assembly, maintenance, and...

The primary cilium is a microtubule-based structure that protrudes from the cell surface in diverse eukaryotic organisms. It functions as a key signaling center that decodes a variety of mechanical and chemical stimuli and plays fundamental roles in development and homeostasis. Accordingly, structural and functional defects of the primary cilium have profound effects on the physiology of multiple organ systems including kidney, retina, and central nervous system. At the core of the primary cilium is the microtubule-based axoneme, which supports the cilium shape and acts as the scaffold for bidirectional transport of cargoes into and out of cilium. Advances in imaging, proteomics, and structural biology have revealed new insights into the ultrastructural organization and composition of the primary cilium, the mechanisms that underlie its biogenesis and functions, and the pathologies that result from their deregulation termed ciliopathies. In this viewpoint, we first discuss the recent studies that identified the three-dimensional native architecture of the ciliary axoneme and revealed that it is considerably different from the well-known '9 + 0' paradigm. Moving forward, we explore emerging themes in the assembly and maintenance of the axoneme, with a focus on how microtubule-associated proteins regulate its structure, length, and stability. This far more complex picture of the primary cilium structure and composition, as well as the recent technological advances, open up new avenues for future research.