Temperature of the body is crucial for the survival of an organism. We all know that. That’s why we panic when our body temperatures start to rise, for example, during a fever. Our bodies are excellent at maintaining homeostasis (or equilibrium). Yet, small changes in temperature are sometimes necessary, for instance, to ward off an infection. These small changes in temperature are brought about by the brain, specifically the hypothalamus, which in diverse ways regulates the overall temperature of the body.
But how does this whole body temperature bring in effects at the cellular level. Consider fever for example. Fever is an increase in body temperature, caused by the brain to enhance the activity of our immune cells while also preventing growth of infectious bacteria and viruses.
This means, somehow the immune cells and perhaps every other cell is responsive to temperature changes. How?
A Class of Temperature Sensing Proteins
A new research paper published in the journal Molecular Cell has reported identification of a class of cellular proteins that are sensitive to temperature changes (1). These proteins are kinases that control processes regulating expression of genes.
In cells, DNA stores genetic information required for the production (expression) of proteins that effect all cellular function. This genetic information must be expressed at the correct time, as otherwise it would lead to havoc in the cells. Therefore, cells have evolved diverse mechanisms by which they regulate gene expression. Just to highlight this point further – improper expression of genes causes diseases. For example, over-expression of a cell division controlling protein (or other oncogenes) called Cyclin-E can cause cancer (2).
Researchers discovered that a class of proteins called CLKs are sensitive to small fluctuations in temperature. When these proteins were purified from cells growing in the lab, their activity decreased with increase in temperature. Change in specifically CLK activity drastically changed the gene expression profile in a human cancerous cell line. This shows that CLKs are sensitive to temperature and this sensitivity has an effect on expression of genes regulated by CLKs (1).
Further in the paper, researchers showed how the CLKs are sensitive to temperature. They show that these CLK proteins change their conformation (structure) when temperature changes. This conformational change dictates whether these proteins are active or not. These proteins are active, at relatively lower temperature, causing a different set of genes to express. At higher temperatures, CLKs are inactivated (due to conformational changes) thereby causing another set of genes to be expressed while some others are silenced. They obtained similar results in mice as well.
In organisms like crocodiles, turtles and alligators, temperature also determines sex of the offspring (3). The researchers thought that CLKs might also be playing a role in this. So they genetically engineered alligator and turtle CLK proteins and observed that these proteins also had the same sensitivity to temperature. This implies that this mechanism could be more general or evolutionarily conserved.
According to the researchers, this discovery could have even widespread implications. In the paper, they write “our work directly connects circadian changes in body temperature with post-transcriptional control of gene expression, which will have a substantial impact on diverse aspects of physiology”. They go on to say that as people age, core body temperature decreases, which could explain changes in gene expression in the ageing population.
“CLK activity is likely to also impact on gene expression in pathological conditions such as hypothermia, septic shock, and fever, or in the slightly warmer tumor microenvironment”, they further add.
- 1.Haltenhof, T. et al. A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression. Molecular Cell (2020). doi:10.1016/j.molcel.2020.01.028
- 2.Erlandsson, F. et al. Abnormal expression pattern of cyclin E in tumour cells. Int. J. Cancer 369–375 (2003). doi:10.1002/ijc.10949
- 3.Lang, J. W. & Andrews, H. V. Temperature-dependent sex determination in crocodilians. J. Exp. Zool. 28–44 (1994). doi:10.1002/jez.1402700105