The Cytoskeleton and Cellular Compartmentation: Cilia as Specialized Cellular Domains

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About this Research Topic

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Background

The eukaryotic cytoskeleton is a complex and highly dynamic network of protein filaments, such as microtubules, actin, intermediate filaments or septins. A myriad of cell functions depend on the cytoskeleton, including cell division, shape, motility, polarity, signaling and intracellular transport. Cytoskeletal dynamics relies on motor proteins sliding along filaments to traffic cell components and remodel cytoskeletal networks in response to a variety of environmental and physiological cues.

The microtubule cytoskeleton is organized around microtubule organizing centers (MTOCs) such as the centrosome, whose mother centriole can, when the right cues are present, nucleate the formation of a cilium. A plasma membrane protrusion undergirded by a nine-fold symmetrical microtubule shaft, or axoneme, whose basic structure is highly conserved from unicellular eukaryotes to mammals. Contrasting with this structural conservation, cilia display great functional versatility. Motile cilia (including the longer and whip-like flagella) enable cells to swim or displace extracellular fluids in tissues. Primary cilia are immotile but work as cellular antennae, sensing tissue-specific signals, such as photons, urine flow, embryonic morphogens or hormones, among many others. In humans, cilia malfunction causes diseases known as ciliopathies which are associated with some types of cancer.

Cilia have been extensively studied in the last decade. However, much critical information regarding their structure and function remains unclear. This applies, for instance, to their tissue-specific functions. The canonical structural pattern of (9+2) and (9+0) for axonemal microtubules is full of exceptions. For example, embryonic nodal cilia are present in monociliated cells. However, whereas in mammals these seem to have a 9+0 pattern, this is not the case for other vertebrates, where variable types of cilia architecture have been found. Cilia variability extends to their base, where poorly characterized basal body-associated structures play important roles, and to their distal domains, where specific cilia tip architectures have been found. How this diversity correlates with tissue-specific cilia functions and associated signaling is far from understood. Recent data point to the possibility that this may be related to specific tissue tubulin isotypes and post-translational isoforms. Tubulin biochemical diversity could explain tissue-specific differences in recruitment of distinct microtubule accessory proteins, alteration of IFT transport, or localization of ciliary receptors and/or signal transducers. Another uncovered point concerns respiratory cilia in multiciliated cells. The wavy beating of these cilia is required for mucociliary clearance. However, It has been shown that integrins and cadherin-like molecules accumulate at the ciliary tip, where their interactions could help explain beating coordination.

This Research Topic aims to shed light on those unanswered questions showcasing relevant studies that address cilia research.

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