What Is The Function of Synapsin Proteins?

By Dillon Lim - Medicine Student @ Brasenose College, Oxford

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Synapsins are a family of proteins, coded for by three genes in humans, that have important roles in controlling synaptic transmission – or the transduction of a signal between two neurons. Signals between nerves are most often carried by neurotransmitters – chemicals stored in phospholipid vesicles. A portion of these vesicles are ‘superprimed’ – they sit right on the presynaptic membrane and are the first to be released when an action potential reaches the presynaptic terminal. Many more vesicles sit further back, in what we call the reserve pool of vesicles. It is clear that synapsins have some role in maintaining the reserve pool, although different synapsins have different effects, and how they maintain the reserve pool is not exactly clear. Some people think that synapsins bind to each other to physically link vesicles to each other, while others think that they maintain a separated phase (i.e. same state of matter but immiscible) within the cytosol.

An additional layer of complexity is added by the fact that different synapsin genes and isoforms play different roles at different synapses. At excitatory synapses which use glutamate (a type of amino acid) as a neurotransmitter, an isoform of Synapsin 2 seems to be the most important in maintaining normal transmission. At inhibitory synapses which use GABA (another amino acid), Synapsin 2 seems to play a much less important role, and Synapsins 1 and 3 are more important. However, we are not yet sure why this is the case! Clearly, there is a lot more work to be done before we really understand the mechanisms for the impacts of synapsins on synaptic behaviour.

Given the importance of synapsins in regulating presynaptic activities, it is not surprising that an increasing amount of research is linking them to psychiatric and neurodegenerative disorders. Synapsins have been implicated in a variety of neurological conditions. In humans, mutated synapsins are associated with some types of epilepsy and schizophrenia. A common type of genetic experiment is called the knock-out – essentially removing a target gene to look at its effect on an organism. Interestingly, mice with either double- or triple-knockouts of synapsin genes are also epileptic! Decreased levels of synapsin gene expression are common to patients with early-stage dementia and with progressed Alzheimer’s disease (a specific type of dementia). Changes in the phosphorylation status of synapsins also appears to be important. Synapsins generally have several sites at which they can be phosphorylated – an enzyme catalyses the addition of a phosphate group to a point on the protein, changing its conformation and therefore its behaviour. We see abnormal changes in synapsin phosphorylation in Huntington’s disease and after transient ischaemia. This latter point might account for some of the pathological changes that follow a cerebrovascular accident (stroke).

Further reading:

1. Synaptic Transmission. https://teachmephysiology.com/nervous-system/synapses/synaptic-transmission/

2. Synapsin Isoforms and Synaptic Vesicle Trafficking. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673407/

3. The Role of Synapsins in Neurological Disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856722/