What is a primary cilium?
Before we can answer this we need some definitions of biological terms:
Epithelial cells : epithelia are sheets of cells that cover many of the body surfaces. The ones we will focus on are those found lining the kidney tubules. As you would guess, kidney tubules are tubular structures inside which urine is made. The individual epithelial cells are held together by “tight junctions”, “adhering junctions” and “desmosomes” ( you don’t need to remember these other than knowing they have a role in controlling flow of particles between neighbouring cells)
Apical surface : each epithelial cell has a top and bottom or an apex and a base. Such a cell is described as polarised. The apical surface is the one facing inwards to the lumen or inside of the tubule.
Cilia : Cilia are appendages found on the surface of cells, specifically on the apical surface.
In mammals there are two types of cilia – called “primary” and “motile”. The motile ones were the first to be discovered; they are responsible for clearing our airways, helping the egg move along the Fallopian tubes and for swimming sperm. Primary cilia, on the other hand, do not move and for many years biologists thought they had no function. Under the microscope the most obvious difference between the two types is in their structure – while both have a backbone of microtubules (internal cylinders from one end to another) the motile cilia also have two extra cylindrical microtubules inside the main ring.
A primary cilium protrudes from the cell, but it is very small in relation to that one cell. A cilium is only about 200-300nm in diameter. The whole renal tubule epithelial cell will be around 50 microns wide, which is 50,000nm.
Because it is very much on the edge of the cell the internal constituents can be quite different from that of the main body of the cell. It contains different proteins and high concentrations of calcium. It also has many proteins fixed to the ciliary membrane which act as transporters and messengers. Two of these are the polycystins, PKD1 and PKD2.
People with ADPKD are known to have defects or absence of one or other of these two polycystin proteins.
There are around 50 known diseases that affect cilia. They are called “ciliopathies“. Because cilia play crucial roles in different parts of the body and at different stages of life, the range of symptoms and pathologies these ciliopathies cause is wide. This is also the explanation behind the involvement of other organs in ADPKD such as liver, bowel, blood vessels etc.
Knowledge about the function of primary cilia increases exponentially year on year. New proteins and ion channels are identified regularly and it is possible that some of these are also involved in ADPKD, not just the known PKD1 and PKD2
One hypothesis says that together the PKD1 and PKD2 conduct calcium through the cell membrane.
Several studies have shown that the two polycystins need each other to perform some of their functions, which is presumably why the end result of loss of either will produce similar pictures. This explains why two different genetic mutations are implicated in ADPKD.
Some recent studies suggest that PKD2 is selective for potassium. Delving a little deeper, research on pkd2 specifically has linked it with other transport proteins and when they combine, such as in the PKD2-L1 complex, the preference for specific ions or chemicals changes. So they become responsible for transporting different ions into the cell, which can alter the electrical potential within the cilium, perhaps changing it’s function dynamically.
It is an expanding field and in the longer term promises the introduction of new treatments for ADPKD.