Multicellular organisms have different cells and tissues doing different things, but also the same signal molecules such as hormones travelling to each cell in the body. Equally, different cells have different receptor molecules, on their surface and inside the cell, and their DNA in the nucleus.
Communication therefore is the connection between these different receptors, whether they are present (if not, the signal simply won’t be read) or not, and the signal molecules. Moreso, signals themselves can cause a production or reduction of receptors in cells. The same signal molecules can also result in different outcomes in different tissues. Welcome to biology!
Since cells are separated by lipid membranes, the route taken for signal transmission can be categorised according to whether the signal molecules act at the cell surface (on the membrane), or straight into the cell. As such, the signals can be hydrophobic or hydrophilic.
Hydrophobic signals: thyroxine; sex hormones
Hydrophobic signals include the hormones thyroxine (secreted by the thyroid gland) and steroids such as testosterone and oestrogen. These chemicals are hydrophobic, like the plasma membrane inner core which contains the hydrophobic phospholipid tails.
They can make their way past cell membranes and act directly on receptors inside the cell. In the case of thyroxine, its receptor protein binds DNA directly, inhibiting the transcription of the gene for Na+/K+ATPase (the previously introduced membrane transport protein responsible for maintaining the ion gradient in nerve signal transduction, kidney function, etc.).
When thyroxine is present, it binds its receptor protein, changing its conformation and resulting in it releasing the DNA at that location. This allows the transcription of the gene for the Na+/K+ATPase pump, raising metabolic rate.
In an opposite way to thyroxine, testosterone activates its receptor to act as a transcription factor for specific genes. It acts in an “opposite” way because its receptor actually initiates transcription, while the thyroxine receptor by default inhibits it. Only when thyroxine is present, the receptor’s inhibiting action is itself inhibited, therefore passively allowing transcription to occur.
Testosterone (converted to its active form dihydrotestosterone or DHT once in the cell) binds its receptor, the phosphorylated (P) androgen receptor (AR), releasing it from heat shock proteins. This allows it to move into the cell nucleus and bind the part of DNA that it governs, initiating transcription of relevant protein products.
Hydrophilic signals: insulin; antidiuretic hormone (ADH, a.k.a. vasopressin)
Hydrophilic signal molecules such as peptide hormones and neurotransmitters cannot cross the plasma membrane, so relay their signal via a transduction pathway through other molecules.
The peptide hormone insulin is a good example. Its receptor is a transmembrane protein that changes conformation, resulting in a change on its side facing inside the cell. This kickstarts multiple metabolic cascades. The receptor’s action (as a tyrosine kinase) involves the phosphorylation of the relevant proteins in these cascades. Don’t worry, no need to memorise all the parts in these cascades!
Examples include the activation of GLUT4 glucose transporter recruitment to the cell membrane to take up blood glucose in fat and muscle cells; glycogen synthesis; glycolysis; and fatty acid synthesis. Exercise can also cause GLUT4 recruitment, improving glucose uptake in people with type 2 diabetes.
Type 1 diabetes is an auto-immune disease that develops early in life. The body destroys the pancreas islet cells responsible for the production of insulin. It is rectified with insulin injections and close monitoring of blood glucose. Advances are being made in recreating the missing cells either by transplantation, stem cell therapy or an implantable artificial device.
Unlike type 1, type 2 diabetes involves a desensitisation to insulin rather than its complete absence. It is associated with obesity and certain other health problems Treatment consists of an improved lifestyle with a better diet and more exercise. If it gets bad, insulin may be needed to supplement the patients’ own insulin.
Aside from activation via phosphorylation, G protein signal transduction (previously covered) and activation of protein cascades is also common with hydrophilic signals. As for ADH (antidiuretic hormone, a.k.a. vasopressin), it binds its receptor (vasopressin receptor/VR) on the membrane, leading to a recruitment of water-transporting AQP2 (aquaporin 2) channel proteins. These allow for balance of water which moves swiftly via the AQP2 channels.
The short term effect is simply directing cytoplasm aquaporins to the membrane. Longer term, the further transcription of more aquaporins is initiated.
A deficiency of ADH or insensitivity to its receptor leads to a condition causing great thirst and increased passing of urine. Due to these symptoms, the otherwise unrelated condition is called diabetes insipidus.