Synaptophysin

Last updated
SYP
Identifiers
Aliases SYP , MRX96, MRXsynaptophysin
External IDs OMIM: 313475 MGI: 98467 HomoloGene: 2391 GeneCards: SYP
Gene location (Human)
Ideogram human chromosome X.svg
Chr. X chromosome (human) [1]
Human chromosome X ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band Xp11.23Start49,187,804 bp [1]
End49,200,259 bp [1]
RNA expression pattern
PBB GE SYP 213200 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003179

NM_009305

RefSeq (protein)

NP_003170

NP_033331

Location (UCSC) Chr X: 49.19 – 49.2 Mb Chr X: 7.64 – 7.65 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Synaptophysin, also known as the major synaptic vesicle protein p38, is a protein that in humans is encoded by the SYP gene. [5] [6]

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Gene basic physical and functional unit of heredity

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Contents

Genomics

The gene is located on the short arm of X chromosome (Xp11.23-p11.22). It is 12,406 bases in length and lies on the minus strand. The encoded protein has 313 amino acids with a predicted molecular weight of 33.845 kDa.

X chromosome The sex chromosome present in both sexes of species in which the male is the heterogametic sex. Two copies of the X chromosome are present in each somatic cell of females and one copy is present in males.

The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system. The X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery.

The unified atomic mass unit or dalton is a standard unit of mass that quantifies mass on an atomic or molecular scale. One unified atomic mass unit is approximately the mass of one nucleon and is numerically equivalent to 1 g/mol. It is defined as one twelfth of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest, and has a value of 1.660539040(20)×10−27 kg, or approximately 1.66 yoctograms. The CIPM has categorised it as a non-SI unit accepted for use with the SI, and whose value in SI units must be obtained experimentally.

Molecular biology

The protein is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38kDa. It is present in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission. It acts as a marker for neuroendocrine tumors, and its ubiquity at the synapse has led to the use of synaptophysin immunostaining for quantification of synapses. [7]

Synaptic vesicle A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the active zone of the presynaptic plasma membrane

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. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.

Glycoprotein protein with oligosaccaride modifications

Glycoproteins are proteins which contain oligosaccharide chains (glycans) covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

Endocrine system system of glands of an organism that secrete hormones directly into the circulatory system to be carried towards distant target organs

The endocrine system is a chemical messenger system consisting of hormones, the group of glands of an organism that secrete those hormones directly into the circulatory system to regulate the function of distant target organs, and the feedback loops which modulate hormone release so that homeostasis is maintained. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The study of the endocrine system and its disorders is known as endocrinology. Endocrinology is a branch of internal medicine.

The exact function of the protein is unknown: it interacts with the essential synaptic vesicle protein synaptobrevin, but when the synaptophysin gene is experimentally inactivated in animals, they still develop and function normally. [8] Recent research has shown, however, that elimination of synaptophysin in mice creates behavioral changes such as increased exploratory behavior, impaired object novelty recognition, and reduced spatial learning. [9]

Synaptobrevin InterPro Domain

Synaptobrevins are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family.

Clinical importance

This gene has been implicated in X linked intellectual disability. [10]

Using immunohistochemistry, synaptophysin can be demonstrated in a range of neural and neuroendocrine tissues, [11] including cells of the adrenal medulla and pancreatic islets. As a specific marker for these tissues, it can be used to identify tumours arising from them, such as neuroblastoma, retinoblastoma, phaeochromocytoma, carcinoid, small-cell carcinoma, medulloblastoma and medullary thyroid carcinoma, among others. Diagnostically, it is often used in combination with chromogranin A. [12]

Immunohistochemistry

Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno", in reference to antibodies used in the procedure, and "histo", meaning tissue. Albert Coons conceptualized and first implemented the procedure in 1941.

Adrenal medulla

The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine in response to stimulation by sympathetic preganglionic neurons.

Neuroblastoma An autonomic nervous system neoplasm that is derived from immature nerve cells.

Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands, but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin.

See also

Interactions

Synaptophysin has been shown to interact with AP1G1 [13] and SIAH2. [14]

Related Research Articles

Synapsin InterPro Family

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. Synapsins are present in invertebrates and vertebrates and are somewhat homologous across evaluated vertebrates.

SNAP25 protein-coding gene in the species Homo sapiens

Synaptosomal nerve-associated protein 25 (SNAP-25) is a t-SNARE protein that is encoded by the SNAP25 gene in humans. SNAP-25 is a component of the trans-SNARE complex, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together.

STX1A protein-coding gene in the species Homo sapiens

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.

RAB3A protein-coding gene in the species Homo sapiens

Ras-related protein Rab-3A is a protein that in humans is encoded by the RAB3A gene. It is involved in calcium-triggered exocytosis in neurons.

DLG3 protein-coding gene in the species Homo sapiens

Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.

VAMP2 protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene.

APBA1 protein-coding gene in the species Homo sapiens

Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.

STXBP1 protein-coding gene in the species Homo sapiens

Syntaxin-binding protein 1 is a protein that in humans is encoded by the STXBP1 gene. This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.

SIAH2 protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase SIAH2 is an enzyme that in humans is encoded by the SIAH2 gene.

CPLX2 protein-coding gene in the species Homo sapiens

Complexin-2 is a protein that in humans is encoded by the CPLX2 gene.

RIMS1 gene of the species Homo sapiens

Regulating synaptic membrane exocytosis protein 1 is a protein that in humans is encoded by the RIMS1 gene.

UBE2L6 protein-coding gene in the species Homo sapiens

Ubiquitin/ISG15-conjugating enzyme E2 L6 is a protein that in humans is encoded by the UBE2L6 gene.

RPH3A gene of the species Homo sapiens

Rabphilin-3A is a protein that in humans is encoded by the RPH3A gene. It contains two C2 domains and binds calcium ions at low micromolar concentration. Rabphilin was shown to regulate neurotransmitter release in hippocampal neurons after neurons had an increased synaptic activity and their release rate was depressed.

DNAJC5 protein-coding gene in the species Homo sapiens

DnaJ homolog subfamily C member 5, also known as cysteine string protein or CSP is a protein, that in humans encoded by the DNAJC5 gene. It was first described in 1990.

CPLX1 protein-coding gene in the species Homo sapiens

Complexin-1 is a protein that in humans is encoded by the CPLX1 gene.

SYPL1 protein-coding gene in the species Homo sapiens

Synaptophysin-like protein 1 is a protein that in humans is encoded by the SYPL1 gene.

SYNPR protein-coding gene in the species Homo sapiens

Synaptoporin is a protein that in humans is encoded by the SYNPR gene.

SYNGR1 protein-coding gene in the species Homo sapiens

Synaptogyrin-1 is a protein that in humans is encoded by the SYNGR1 gene.

Synapsin I protein-coding gene in the species Homo sapiens

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. Synapsin I is the first of the proteins in the synapsin family of phosphoproteins in the synaptic vesicles present in the central and peripheral nervous systems. Synapsin Ia and Ib are close in length and almost the same in make up, however, Synapsin Ib stops short of the last segment of the C-terminal in the amino acid sequence found in Synapsin Ia.

Synapsin 2 protein-coding gene in the species Homo sapiens

Synapsin II is the collective name for synapsin IIa and synapsin IIb, two nearly identical phosphoproteins in the synapsin family that in humans are encoded by the SYN2 gene. Synapsins associate as endogenous substrates to the surface of synaptic vesicles and act as key modulators in neurotransmitter release across the presynaptic membrane of axonal neurons in the nervous system.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102003 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031144 - Ensembl, May 2017
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
  5. "Entrez Gene: SYP synaptophysin".
  6. Südhof TC, Lottspeich F, Greengard P, Mehl E, Jahn R (November 1987). "The cDNA and derived amino acid sequences for rat and human synaptophysin". Nucleic Acids Res. 15 (22): 9607. doi:10.1093/nar/15.22.9607. PMC   306499 . PMID   3120152.
  7. Calhoun ME, Jucker M, Martin LJ, Thinakaran G, Price DL, Mouton PR (December 1996). "Comparative evaluation of synaptophysin-based methods for quantification of synapses". J. Neurocytol. 25 (12): 821–8. doi:10.1007/BF02284844. PMID   9023727.
  8. McMahon HT, Bolshakov VY, Janz R, Hammer RE, Siegelbaum SA, Südhof TC (May 1996). "Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release". Proc. Natl. Acad. Sci. U.S.A. 93 (10): 4760–4. doi:10.1073/pnas.93.10.4760. PMC   39352 . PMID   8643476.
  9. Schmitt U, Tanimoto N, Seeliger M, Schaeffel F, Leube RE (August 2009). "Detection of behavioral alterations and learning deficits in mice lacking synaptophysin". Neuroscience. 162 (2): 234–43. CiteSeerX   10.1.1.320.5309 . doi:10.1016/j.neuroscience.2009.04.046. PMID   19393300.
  10. Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer AP, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR (May 2009). "A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation". Nat. Genet. 41 (5): 535–43. doi:10.1038/ng.367. PMC   2872007 . PMID   19377476.
  11. Wiedenmann, B; Franke, WW; Kuhn, C; Moll, R; Gould, VE (May 1986). "Synaptophysin: a marker protein for neuroendocrine cells and neoplasms". Proceedings of the National Academy of Sciences of the United States of America. 83 (10): 3500–4. doi:10.1073/pnas.83.10.3500. PMC   323544 . PMID   3010302.
  12. Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 405–406. ISBN   978-1-84110-100-2.
  13. Horikawa HP, Kneussel M, El Far O, Betz H (November 2002). "Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin". Mol. Cell. Neurosci. 21 (3): 454–62. doi:10.1006/mcne.2002.1191. PMID   12498786.
  14. Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L (March 2002). "Regulation of synaptophysin degradation by mammalian homologues of seven in absentia". J. Biol. Chem. 277 (12): 10273–82. doi:10.1074/jbc.M107857200. PMID   11786535.

Further reading