The interior structure of eukaryotic (human and animal) cells is well known. For our purposes, for tumorigenesis, we focus on centrioles - a small pair of perpendicular cylinders adjacent to the nucleus. Errors in centriole geometry are believed to be a source of tumorigenesis .
The centrioles are distinctly different from all other organelles and organs:
1) They have precise geometry
2) They have no membrane cover
3) They may be viewed as hollow cylinders with nine radial blades, each having themselves three hollow cylinders known as “microtubules”, forming the centriole circumference
4) Viewed as a cylinder, each centrioles is approximately 400 to 500 nm long and 200 nm in diameter
5) Centrioles occur in pairs (often called the “mother” and “daughter”) with the daughter being perpendicular to the mother and attached to the mother at the base
6) The centrioles lie in a cloud of many proteins which together with the centrioles is known as the “centrosome”
Figure 1 provides a sketch of a typical centriole pair.Figure 1:
A Typical centriole pair and their centriolar blades.
The centrioles play a central role in cell division. Although this process is generally well understood it may be helpful to some readers to briefly review the cell cycle (birth to separation) [29-33]. The cycle may be viewed in two phases: the “M-phase” (mitosis) and the “interphase” as represented in figure 2.Figure 2:
The M-phase consists of several subphases called: “Prophase”; “Metaphase”; “Anaphase”; “Telophase”; and “Cytokinesis”. This set of subphases is also known as “mitosis”. Curing mitosis the nucleus is divided and the chromosomes are separated. The cytoplasms with its various organelles are also separated into two halves, each half following one of the nucleus halves.
The Interphase, which is considerably longer than the M-phase also consists of several phases: G1 (or “Gap1”) for growth; S-phase, for more growth and DNA duplication; and G2 (or “Gap2”) for still more growth and for preparation for division.
During the S-phase the centrioles are also duplicated into two pairs, and then during prophase the centriole pairs are separated with the newer pair moving to the opposite side of the nucleus. The centriole pairs now on opposite sides of the nucleus extend their microtubules to form the mitotic spindle, and then pull apart the nucleus [29-33].
As noted previously the centrioles are composed of nine “blades” of Microtubules (MTs) with each blade having three MTs. Thus each centriole has a total of 27 parallel MTs, and some centrioles have an additional two MTs along their axes.
For a typical blade of MTs, each MT does not have the same length: The interior MT (closest to the centriole axis) is the longest. The exterior MT (closest to the centriole perimeter) is the shortest. The third MT then has intermediate length. They are labeled: “A”, “B”, and “C” as represented in figure 3.Figure 3:
New (“daughter”) centrioles are grown from the side at the base of the “mother” centriole, with the axis of the daughter being perpendicular to the axis of the mother. The daughter growth begins on the exterior side of one of the C-MTs.
With there being nine C-MTs, it is not clear which is to be selected for the base of the daughter centriole.
The growing process is believed to occur as follows: During the S-phase of the cell cycle, as the DNA is being separated, a small quantity of Asterless (AsP) is deposed at the base of the selected C-MT. (AsP is the orthologue of Cep152 . The AsP/Cep152 then recruits a patch of the polo-like kinase enzyme: Plk4 which then in turn recruits the protein: SAS-6 for the base of the ensuing daughter centriole.
SAS-6 projects nine outward spokes whose ends attract three spots of Gamma (ϒ) tubulin. The ϒ-Tubulin Ring Complex (ϒTu-RC) and the ϒ-Tubulin Small Complex (ϒTu-SC) [7,35-43].
Figure 4 provides a simplified representation of this process.Figure 4:
A microtubule, the Gamma-Tubulin Ring Complex (ϒTu-RC) and the Gamma-Tubulin Small Complexes (ϒTu-SCs).