Synaptic signal complexes: Information transfer in the central nervous system

Nerve cells are involved in everything we do – not only when we move but also whenever we see, hear, think, or remember something. Nerve cells, for example, transmit sensory data from the eye or the ear to specialised centres in the brain, where these activity patterns are processed by other nerve cells and we become aware of them. However, signal transfer in the nervous system is not as easy as in an electric circuit when you press a switch and the current starts to flow. A large number of proteins are responsible for processing signals in the nervous system and are the subject of research carried out by Prof. Dr. Ralf Enz, professor of biochemistry and medical molecular biology at FAU and his team. They are investigating the interaction between proteins in the central nervous system, for example in the retina in the eye, and the cochlea, the part of the inner ear that picks up auditory signals and passes them on to the brain. Their aim is to discover how signalling pathways work in these sensory tissues and how disruptions lead to disorders such as blindness, deafness or tinnitus.

Signal transduction – interaction between proteins

Synapses, or connections between nerve cells, are crucial during signal transduction between nerve cells. In this process, messenger substances are released from the axon terminals of the first cell, which is also known as the presynapse. These messenger substances or neurotransmitters diffuse across the synaptic cleft to the receptors on the next cell, known as the postsynapse. The docking of the neurotransmitter onto the receptor either excites or inhibits the downstream nerve cell, depending on the receptor type.

This may sound simple at first, but in reality it is much more complex, explains Enz. Some neurotransmitter receptors have their own ion channels. These tube-shaped proteins guide particles with an electric charge, or ions, into the cell when it opens. A bond between the neurotransmitter and these receptors thus leads directly to a change in the state of excitation of the nerve cells. Other neurotransmitter receptors, on the other hand, do not have an ion channel, but regulate the activity of signalling cascades. Different receptors dock on to different signalling cascades, which, in turn, regulate different cellular processes such as the opening or closing of further ion channels or gene expression, for example the formation of proteins.

An additional level of complexity of chemical synapses is underlined by the fact that neurotransmitter receptors do not function in isolation. In the same way that individual musicians in an orchestra play together in the same physical space and time, a large number of proteins are precisely coordinated for synaptic signal transfer. Anchoring proteins ensure that the receptors stay in their intended location in the area of the synapses. Adapter proteins ensure close spatial proximity between the proteins during signal transduction to keep the process running smoothly and efficiently. Other proteins control the quantity of neurotransmitter receptors on the synapses and regulate their activity. Together, all the proteins that interact in this way are known as a synaptic signal complex. Disruptions to the structure or regulation of these synaptic signal complexes can lead to malfunctions and illness.

Mapping signal complexes

Enz and his team investigate these synaptic signal complexes in the retina and cochlea and analyse which receptor types are located on which synapses. They look for new proteins that bind to and regulate these neurotransmitter receptors, forming part of synaptic signal complexes. Their research also involves investigating newly identified binding partners in terms of the activity of the receptors, the quantity of receptors on the cell surface and the effects of receptors coupled to signalling cascades. In addition, they describe the physical structures of contact surfaces between receptors and their newly-identified binding partners. The FAU researchers are basically developing maps of these synaptic signal complexes, thereby creating the basis for identifying disruptions to the information transfer process in the central nervous system. Their work is making a significant contribution to finding modes of intervention for regulating the synaptic signal complexes and thus for finding new possibilities for treating neurological disorders.

FAU research magazine friedrich

This article first appeared in our research magazine friedrich. You can order the print issue (only available in German) free of charge at presse@fau.de.