Cellular Signalling and Transport
Communication between neurons has a bearing on everything we do, from seeing and remembering our children's faces to being able to walk across the room.
Neurons contact each other at synapses, highly specialised signalling apparatus comprising complex protein structures on the sending and receiving cells. For neuronal networks to function correctly, this molecular assembly must send signals and also modulate their strength and duration.
Synapses are continually being formed, broken and renewed throughout life; indeed this is thought to underlie learning and memory. To maintain synapses, neurons must traffic the necessary protein components from their cell body down long, thin cellular extensions to these distant sites. This transport process is fundamental to neuronal and synaptic activity but is particularly vulnerable to damage resulting in the deterioration of contacts and ultimately neuronal death. The effects of synapse loss are clinically wide-ranging and devastating, including memory loss, dementia and movement disorders.
Neurons are often highly elongated cells, with long axons terminated by connections or 'synapses' with other cells. It is at these synapses that neurons pass information to one another, allowing the brain to perform a myriad of functions, ranging from making sense of our senses, to controlling the movement of our muscles.
Nerve impulses travel the length of an axon before triggering the release of neuro-transmitters at the synapse. Neighbouring neurons detect these transmitters using specialised receptors on their surface and are induced to create a new nerve impulse themselves, thus continuing the signal. This process is tightly controlled by a number of proteins in the neuron. How these 'signalling' proteins act to coordinate this process is a focus of research at the Peninsula Medical School as it is known that loss of functional synapses is a key factor in neuro-degeneration and resultant diseases such as dementia.
For synapses to be properly maintained, an array of signalling and structural proteins have to be transported within the neuron and delivered to the correct destination for their function. The importance of this process is underscored by Spinal Muscular Atrophy, a muscle wasting disease which has been linked by researchers at PMS to defects in axonal transport.
The complex network of neurons in the brain is generated by the formation of axonal extensions (see Cellular Morphology and Migration). This process itself relies upon the delivery of guidance receptors and adhesion molecules to the growing tip of the axon. How these proteins are delivered and recycled is also a central research theme of the group.
Not only is cell signalling and adhesion required for the formation of functional neuronal networks, but when improperly controlled, can lead to the generation of tumours. For example, Schwannomas are tumours caused by defects in the ability of Schwann cells to process signals that control how they interact with their local environment. Research at PMS is demonstrating how particular signalling proteins are involved in this process and ultimately identifying potential drug targets.