Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells
Posted on: 19 January 2019 , updated on: 20 January 2019
Preprint posted on 4 December 2018
Categories: biochemistry, biophysics, cell biology, genetics, molecular biology, pathology, physiology
Background
Our airways are lined by billions of hair-like projections called cilia which beat in concerted motion to propel mucus through the respiratory tract. This mucociliary clearance moistens and protects the airway and is thus important for health and disease [1]. Whereas most cells in the body form only one sensory primary cilium, from a microtubule organising structure called a basal body (or centrosome), airway epithelial cells each form hundreds of motile cilia from hundreds of basal bodies (Fig. 1). In general, cilia are thought to be either sensory, transducing signals into the cell, or motile, and thus capable of producing physical force. In a recent preprint, the ultrastructure and position of cilia in multiciliated airway epithelial cells has been investigated. The authors suggest the presence of a hybrid cilium with features of both primary and motile cilia, which is positioned relative to mucociliary fluid flow.
Key findings
Spatial arrangement of cilia basal foot proteins
The positions of proteins found in a protrusion of the basal body called the basal foot were mapped with super-resolution light microscopy. Comparative analysis of the spatial arrangement of basal foot proteins in primary cilia versus motile cilia shows that whereas some basal foot proteins remain in the same spatial arrangement dependent on cilia type, others change location with concomitant ultrastructural changes.
A novel hybrid cilium as a signalling centre and flow sensor
Using focused ion beam scanning electron microscopy, the authors show that whereas primary cilia have multiple basal feet per basal body, in multiciliated epithelial cells two different types of basal foot arrangement exist. Motile cilia in multiciliated epithelial cells have one basal foot, with the exception of a “hybrid” motile cilium, which is formed from the original parental centrosome and has multiple basal feet. Mapping of the position of this hybrid cilium within each cell shows that it orientates towards the direction of ciliary beating. Dynein mutations causative of primary ciliary dyskinesia with impaired ciliary beating and mucociliary clearance, disrupt this hybrid cilium positioning.
What I like about this preprint
The basal body must dynamically adapt to different cellular states, templating different types of cilia during differentiation. This preprint systematically examines basal body structure in different cellular states by mapping basal foot components in primary versus motile cilia. Interestingly, another preprint released a day earlier examines basal body duplication in multiciliated airway epithelia [2], finding a correlation between cilia number and cell surface area. Thus, airway multiciliated epithelial cells adjust basal body number and position in response to physiological conditions such as fluid flow and tissue patterning. This might have implications for understanding fundamental mechanisms of organelle number and position control, and how we might treat airway disease in the future.
Questions
Why do human airway multiciliated cells have different types of cilia (motile and hybrid)?
Why is hybrid cilium subcellular position adjusted relative to fluid flow?
How is hybrid cilium subcellular position adjusted relative to fluid flow?
What functional properties are endowed upon a cilium by the arrangement of basal foot proteins?
What spatial arrangement of basal foot proteins would be predicted after knockout of CTRLN?
References
1. Tilley AE, Walters MS, Shaykhiev R, Crystal RG. (2014). Cilia dysfunction in lung disease. 77:379-406.
2. Nanjundappa R, Kong D, Shim K, Stearns T, Brody SL, Loncarek J, and Mahjoub MR. (2018). Regulation of Cilia abundance in multiciliated cells. doi 10.1101/478297.
doi: https://doi.org/10.1242/prelights.7648
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