Synapsin 2
Encyclopedia
Synapsin II is the collective name for Synapsin IIa and Synapsin IIb, two nearly identical phosphoprotein
s in the synapsin
family that in humans are encoded by the SYN2 gene
. Synapsins associate as endogenous substrates to the surface of synaptic vesicle
s and act as key modulators in neurotransmitter
release across the pre-synaptic membrane of axon
al neurons in the nervous system.
gene is located within an intron
of this gene and is transcribed in the opposite direction.
family. Synapsins encode neuronal phosphoprotein
s which associate with the cytoplasmic surface of synaptic vesicle
s. Family members are characterized by common protein domain
s, and they are implicated in synaptogenesis and the modulation of neurotransmitter
release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron
-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal.
Synapsin II the collective name for two proteins, Synapsin IIa and Synapsin IIb, with Synapsin IIa being the larger of the two isoforms. Their apparent molecular weights are 74,000 and 55,000 per SDS gel electrophoresis. Synapsin II along with Synapsin I comprise approximately 9% of the proteins in highly purified samples of synaptic vesicles.
Synapsin IIa is the only Synapsin isoform of the six Synapsin isoforms (Synapsin I-III each with isoforms A and B), which has been shown to significantly reverse synaptic depression and has a restorative effect on the density of synaptic vesicles within Synapsinless neurons. Because of its restorative effect on the density of synaptic vesicles and ability to restore the otherwise depressed synaptic response in neurons lacking pre-existing Synapsins, Synapsin IIa is believed to play a fundamental role in synaptic vesicle mobilization and reserve pool regulation in the presynaptic nerve terminal. Lack of Synapsins altogether in neurons, leads to behavioral alterations as well as epileptic type seizures. The lack affects nervous signal transduction across excitatory and inhibitory synapses of neurons differently and is believed to be synapse specific. Initial signal transduction appear to be unaffected by the lack of Synapsins, but repeated stimulation of cultured Synapsinless hippocampal neurons, subsequently showed depressed responses at the excitatory synapse. At the inhibitory synapse, base signal transduction is reduced in neurons lacking pre-existing Synapsins, but the reduced level of transduction is less affected by progressive stimulation.
However, the restoration of Synapsin IIa to neurons without pre-existing Synapsins, can partially recover presumably lost signal transduction and slow the depression of synaptic response with progressive stimulation. Its isoform Synapsin IIb, may have a similar but weaker effect. Through fluorescence and staining, it has been demonstrated that Synapsin IIa, increases the number and density of glutamatergic synaptic vesicles in the nerve terminal of neural axons. The recovery of nervous signal transduction is attributed to the increase in density of synaptic vesicles, which carry neurotransmitters to the synaptic cleft, and the amount of synaptic vesicles in the reserve pool in the presence of Synapsin IIa. In turn, this is thought to increase the number of vesicles available for mobilization from the reserve pool to the ready-release pool. The reserve pool is the pool of synaptic vesicles which reside in the nerve terminal away from the presynaptic membrane of the axon, but are not in the ready to release or ready-release pool. Those vesicles in the ready-release pool reside very close to the presynaptic membrane and are primed to release neurotransmitters for nervous signal transduction.
with SYN1
.
s in the SYN2 gene may be associated with abnormal presynaptic function and schizophrenia
.
Phosphoprotein
Phosphoproteins are proteins that are physically bonded to a substance containing phosphoric acid . This category of organic molecules includes Fc receptors, Ulks, Calcineurins, K chips, and urocortins....
s in the synapsin
Synapsin
The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.Current studies suggest...
family that in humans are encoded by the SYN2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Synapsins associate as endogenous substrates to the surface of synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s and act as key modulators in neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
release across the pre-synaptic membrane of axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
al neurons in the nervous system.
Gene
Alternative splicing of the SYN2 gene results in two transcripts. The TIMP4TIMP4
Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
gene is located within an intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
of this gene and is transcribed in the opposite direction.
Protein
Synapsin II is a member of the synapsinSynapsin
The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.Current studies suggest...
family. Synapsins encode neuronal phosphoprotein
Phosphoprotein
Phosphoproteins are proteins that are physically bonded to a substance containing phosphoric acid . This category of organic molecules includes Fc receptors, Ulks, Calcineurins, K chips, and urocortins....
s which associate with the cytoplasmic surface of synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s. Family members are characterized by common protein domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
s, and they are implicated in synaptogenesis and the modulation of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal.
Synapsin II the collective name for two proteins, Synapsin IIa and Synapsin IIb, with Synapsin IIa being the larger of the two isoforms. Their apparent molecular weights are 74,000 and 55,000 per SDS gel electrophoresis. Synapsin II along with Synapsin I comprise approximately 9% of the proteins in highly purified samples of synaptic vesicles.
Structure
Synapsin II shares common domains within its amino acid sequence with other phosphoproteins in the Synapsin family. Sharing the same N-terminal, Synapsin II diverges from Synapsin I in its C-terminal domains. It is much shorter than Synapsin I and is missing most of the elongated domains seen in Synapsin I. Roughly 70% of the amino acid residues are common between the two Synapsins and share common phosphorylation sites in the overlapping regions based on the homologous domains. Domain A of this neural protein contains phosphorylation sites for cAMP dependent protein kinase and calcium/calmodulin dependent protein kinase I and domain B has two mitogen-activated protein kinase phosphorylation sites. At protein's domain B, between amino acids 43 and 121 of the protein's sequence, Synapsin II binds to a protein component in the cytosolic surface membrane of synaptic vesicles, organelles in neurons which carry neurotransmitters.Function
Synapsin II regulates synaptic function of neurons in the central and peripheral nervous system. These phosphoproteins like the others in the Synapsin family, are found associated with the membrane of synaptic vesicles in the pre-synaptic nerve terminal of axons.Synapsin IIa is the only Synapsin isoform of the six Synapsin isoforms (Synapsin I-III each with isoforms A and B), which has been shown to significantly reverse synaptic depression and has a restorative effect on the density of synaptic vesicles within Synapsinless neurons. Because of its restorative effect on the density of synaptic vesicles and ability to restore the otherwise depressed synaptic response in neurons lacking pre-existing Synapsins, Synapsin IIa is believed to play a fundamental role in synaptic vesicle mobilization and reserve pool regulation in the presynaptic nerve terminal. Lack of Synapsins altogether in neurons, leads to behavioral alterations as well as epileptic type seizures. The lack affects nervous signal transduction across excitatory and inhibitory synapses of neurons differently and is believed to be synapse specific. Initial signal transduction appear to be unaffected by the lack of Synapsins, but repeated stimulation of cultured Synapsinless hippocampal neurons, subsequently showed depressed responses at the excitatory synapse. At the inhibitory synapse, base signal transduction is reduced in neurons lacking pre-existing Synapsins, but the reduced level of transduction is less affected by progressive stimulation.
However, the restoration of Synapsin IIa to neurons without pre-existing Synapsins, can partially recover presumably lost signal transduction and slow the depression of synaptic response with progressive stimulation. Its isoform Synapsin IIb, may have a similar but weaker effect. Through fluorescence and staining, it has been demonstrated that Synapsin IIa, increases the number and density of glutamatergic synaptic vesicles in the nerve terminal of neural axons. The recovery of nervous signal transduction is attributed to the increase in density of synaptic vesicles, which carry neurotransmitters to the synaptic cleft, and the amount of synaptic vesicles in the reserve pool in the presence of Synapsin IIa. In turn, this is thought to increase the number of vesicles available for mobilization from the reserve pool to the ready-release pool. The reserve pool is the pool of synaptic vesicles which reside in the nerve terminal away from the presynaptic membrane of the axon, but are not in the ready to release or ready-release pool. Those vesicles in the ready-release pool reside very close to the presynaptic membrane and are primed to release neurotransmitters for nervous signal transduction.
Interactions
The synapsin II protein has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with SYN1
Synapsin I
Synapsin I, is the collective name for Synapsin Ia and Synapsin Ib, two nearly identical phosphoproteins that in humans are encoded by the SYN1 gene. In its phosphorylated form, Synapsin I may also be referred to as phosphosynaspin I...
.
Clinical significance
MutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the SYN2 gene may be associated with abnormal presynaptic function and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.