A centriole's subdistal appendages: contributions to cell division, ciliogenesis and differentiation

Abstract

The centrosome is a highly conserved structure composed of two centrioles surrounded by pericentriolar material. The mother, and inherently older, centriole has distal and subdistal appendages, whereas the daughter centriole is devoid of these appendage structures. Both appendages have been primarily linked to functions in cilia formation. However, subdistal appendages present with a variety of potential functions that include spindle placement, chromosome alignment, the final stage of cell division (abscission) and potentially cell differentiation. Subdistal appendages are particularly interesting in that they do not always display a conserved ninefold symmetry in appendage organization on the mother centriole across eukaryotic species, unlike distal appendages. In this review, we aim to differentiate both the morphology and role of the distal and subdistal appendages, with a particular focus on subdistal appendages.

Keywords: centrosome; cilia; ciliopathies; division; midbody; subdistal appendages.

Figure 1.

The centrosome comprises two centrioles which inherently differ in both age and structure. (a) Side view of a human retinal pigment epithelial cell centrosome schematic with the oldest centriole (mother, grey barrel with blue and purple appendages) and the younger centriole (daughter, light blue barrel devoid of appendages) surrounded by pericentriolar material (PCM, pink). (b) Top-down view of centrosome schematic with the oldest centriole presenting with ninefold symmetry of both distal (purple) and subdistal* (blue) appendages. *Note: We are depicting ninefold symmetry of the subdistal appendages found within human retinal pigment epithelial cells, but subdistal appendage number can change due to extracellular cues and vary across cell types within a single species. (c) Venn diagram highlighting a number of proteins known to localize to either distal appendages (purple), subdistal appendages (blue) or both appendage structures (denoted with arrow pointing to overlapping region).

Figure 2.

The cytokinetic midbody directing ciliogenesis. (a) Ciliated epithelium with cilia at the apical membrane. (b) When cells decide to enter division and duplicate their centrosomes the cilia are disassembled, and the centrioles duplicate to make two mitotic spindle poles. With one mitotic centrosome containing the oldest centriole (grey barrel with blue and purple appendages, noted as the mother) that has associated appendages. (c) The two mitotic centrosomes that are inherently asymmetric due to centriole age assemble the bipolar microtubule-based spindle. (d) As cells progress through anaphase and cytokinesis a cytokinetic bridge is formed with an associated midbody (green dot). (e) As the cells abscise the bridge the midbody can still be attached and marks a place on the apical membrane where the cell with the oldest mother centriole will grow a cilium first.

Figure 3.

Asymmetric neuro divisions associate with a cilia remnant. The figure summarizes the relationship between a cilium in a neuro stem cell that will undergo an asymmetric neurogenic division (neurogenic divisions modelled from [33]). The dividing cell inherits a remnant of the cilium at the mitotic centrosome with the oldest mother centriole, which is usually the cell that remains stem and forms a cilium first. The other cell then goes on to differentiate.

Figure 4.

Appendage proteins result in cilia defects and/or spindle positioning defects with downstream consequences to development. CC2D2A (green) loss results in cilia loss, but no reported cell cycle defects. Cenexin and centriolin (blue) when lost cause defects in cilia formation and mitotic progression/spindle positioning, whereas loss of ninein (magenta) results in mitotic spindle defects (e.g. prometaphase/metaphase arrest and spindle positioning errors). Loss of any appendage protein (cenexin, CC2D2A, centriolin or ninein) results in severe developmental defects.