What Are Receptors?
Two Antennas Got Married …
The ceremony wasn't much, but the reception was excellent.
Sorry, I couldn't resist. It's just that, as it happens, we're going to talk about two ‘antennas'.
OK, you read in the degranulation post that mast cells have like little antennas on their surface, called receptors. These receptors are waiting for a signal that tells the mast cell that our bodies are under attack. And you saw the video which showed little blue Y-shaped poles sticking out of the cell membrane. I'll spare you the details, but just know that in that Y-shaped pole, there is a receptor.
You'll remember we called this Y-pole the antibody and that the ‘signal' the ‘antenna' or receptor received was called the antigen. The result of the antigen touching (called ‘binding') the antibody had the effect of triggering a degranulation event.
Don’t Touch My Antenna, Or Else …
All “antennas” (receptors) belong to one of many families of antennas (receptors) and each receptor does have its own name. That antigen antenna? Its scientific name is IgE, which stands for Immunoglobulin E.
One of the roles of receptors is to do precisely what the antigen (aka. IgE receptor) did in the degranulation event. A receptor just sits there atop the cell membrane, minding its own business sensing the outside world, and when something touches the receptor, it transmits a signal to the inside of the cell and the cell acts on that signal.
The receptor only reacts to things that it likes, though. It only connects (binds) with things (ligands) that have a shape matching the shape of the receptor. It's like a space ship docking to a space station. Both the ship and the station need to have matching docking pieces for that connection to happen.
Let's pause a bit and watch a receptor (in this case, interleukin 1 receptor) bind with its corresponding interleukin1 signalling molecule.
The whole (simplified) process above is called cell signalling. It's a quite bit more elaborate than that, but you get the picture : an external stimuli signals the receptor, which in turn signals the cell, which in turn processes the signal and does something as a result. That “doing something” could be to manufacture yet another ‘something' using machinery within the cell or to create a clone of the cell or to commit cell suicide, among numerous other things. Or, in the case of a mast cell … to degranulate!
Receptors, Receptors Everywhere …
So you've met your first receptor, IgE, the one that causes mast cell degranulation.
But, truth be told, there are many receptor types and a cell's surface is covered with hundreds of receptors of each of the different receptor types. You've briefly met the Interleukin 1 (Il1) receptor in the video above, which was useful just to show you the binding process.
However, forget Il1 for a moment, because the second receptor I'd like to draw your attention on is the infamous c-KIT. It is infamous because it is the cause of all the mastocytosis problems.
The c-KIT is the receptor that causes mast cells to proliferate in an uncontrolled fashion.
The c-KIT is the ‘antenna' which receives the signal which tells the mast cell that it must reproduce itself. When the c-KIT antenna receives that signal (which is called Stem Cell Factor), the c-KIT switches on some machinery inside the cell which causes it to split and ‘give birth' to one more incarnation of a mast cell.
The Ninja Mutant Mastos.
But here's the rub. In some people, the c-KIT receptor is broken. When the c-KIT was manufactured, one piece was incorrectly mounted. Either that, or during time, the c-KIT machinery broke in one particular place. That break, that defect is called a mutation.
The c-KIT mutation is a defect in the receptor, which has the effect of leaving the mast cell production machinery switch on all the time. That means that the mast cell reproduces itself, even though no signal was received to do so. That causes abnormal mast cell proliferation, which is the hallmark of mastocytosis.
As you will learn later in “The Diagnosis” section of this site, the c-KIT mutation is only a minor factor in the diagnosis of mastocytosis. 80 to 90% of mastocytosis sufferers exhibit what is commonly called ‘the D816V' c-KIT mutation. But absence of ‘the D816V' mutation does not preclude having mastocytosis. The reason is that there are 100's of c-KIT mutations which are likely to have the same aberrant proliferation effect, but only very few of those mutations can be effectively tested and detected.
For example, my partner Ann does not have ‘the D816V c-KIT mutation they are testing for. But she still has been diagnosed with mastocytosis. Which means she probably has ‘an XYZ' mutation in the c-KIT, but it cannot be detected by currently available tests.
Knowledge is Power
So, there you have it. You now know the source of mastocytosis (your c-KIT having a mutation) and, although we have not yet reached the section of this site which talks about the symptoms, the reason why you experience mastocytosis symptoms (an antigen hitting IgE receptor and causing mast cell degranulation).