Microtubule‐associated proteins and emerging links to primary cilium structure, assembly, maintenance, and disassembly

Abstract

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.

Primary Cilia Formation Does Not Rely on WNT/β-Catenin Signaling

“…Regulation of ciliogenesis is a complex process involving multiple factors directly or indirectly influencing cilia initiation and elongation. The regulators of cilium formation encompass a wide range of molecules such as components of centrioles, regulators of vesicular trafficking, intraflagellar transport proteins, membrane proteins, and components of cytoskeleton (Seeley and Nachury, 2010;Ishikawa and Marshall, 2017;Wang and Dynlacht, 2018;Conkar and Firat-Karalar, 2020). WNT3a is considered a prototypical "canonical" WNT ligand that activates WNT/β-catenin pathway (Willert et al, 2003).…”

Primary cilia formation does not rely on WNT/β-catenin signaling

“…Regulation of ciliogenesis is a complex process involving multiple factors directly or indirectly influencing cilia initiation and elongation. The regulators of cilium formation encompass a wide range of molecules such as components of centrioles, regulators of vesicular trafficking, intraflagellar transport proteins, membrane proteins and components of cytoskeleton (Wang and Dynlacht 2018; Conkar and Firat-Karalar 2020; Ishikawa and Marshall 2017; Seeley and Nachury 2010).…”

Centrosome Dynamics and Its Role in Inflammatory Response and Metastatic Process

“…Large-scale proteomic studies have revealed that there are more than 400 centrosome-associated proteins (about 3% of human proteome, but the exact functions of most of these proteins are still unknown and require further investigation. However, recent advances in imaging, proteomics, and structural biology have revealed new insights into how microtubule-associated proteins regulate the structure, length, and stability of centrosome/cilium complex opening up new avenues for future research [ 8 , 26 , 27 , 28 ].…”

“…Shared pathways ensure the coordination between centrosome dynamics, chromosome replication–segregation cycles, and ciliogenesis. Details on the centrosome/cilia dynamins can be found in recent excellent reviews [ 8 , 21 , 23 , 26 , 27 ]. ( B ) Excess of expression of centrosome genes (structural changes) can disrupt apical cell extrusion, instead, causing aberrant basal extrusion.…”