The synapsins are a family of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s that have long been implicated in the regulation of
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
release at
synapse
In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
s. Specifically, they are thought to be involved in regulating the number of
synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are exocytosis, released at the chemical synapse, synapse. The release is regulated by a voltage-dependent calcium channel. Vesicle (biology), Ves ...
s available for release via
exocytosis
Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
at any one time.
Synapsins are present in
invertebrates
Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordate subphylum ...
and
vertebrates
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
and are strongly conserved across all species.
They are expressed in highest concentration in the nervous system, although they also express in other body systems such as the reproductive organs, including both eggs and spermatozoa. Synapsin function also increases as the organism matures, reaching its peak at sexual maturity.
Current studies suggest the following hypothesis for the role of synapsin: synapsins bind synaptic vesicles to components of the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
which prevents them from migrating to the
presynaptic membrane and releasing
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
. During an
action potential
An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...
, synapsins are
phosphorylated
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writt ...
by
PKA
In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction
:H ...
(cAMP dependent protein kinase), releasing the synaptic vesicles and allowing them to move to the membrane and release their
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
.
Gene knockout
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
studies in mice (where the mouse is unable to produce synapsin) have had some surprising results. Consistently, knockout studies have shown that mice lacking one or more synapsins have defects in synaptic transmission induced by high‐frequency stimulation, suggesting that the synapsins may be one of the factors boosting release probability in synapses at high firing rates, such as by aiding the recruitment of vesicles from the reserve pool.
Furthermore, mice lacking all three synapsins are prone to seizures, and experience
learning
Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, Attitude (psychology), attitudes, and preferences. The ability to learn is possessed by humans, non-human animals, and ...
defects.
These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role. Lastly, observed effects seemed to vary between inhibitory and excitatory synapses, suggesting synapsins may play a slightly different role in each type.
Family members
Humans and most other
vertebrate
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
s possess three genes encoding three different synapsin proteins.
Each gene in turn is
alternatively spliced
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
to produce at least two different
protein isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
s for a total of six isoforms:
Different neuron terminals will express varying amounts of each of these synapsin proteins and collectively these synapsins will comprise 1% of the total expressed protein at any one time.
Synapsin Ia has been implicated in
bipolar disorder
Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
and
schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
.
References
{{Nerve tissue protein
Molecular neuroscience
Protein families
Peripheral membrane proteins