Synaptophysin

Gene

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.

Tissue distribution

It is expressed in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission.

Structure

The protein is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38 kDa.

Function

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. 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.

Clinical significance

Biomarker

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.

Using immunohistochemistry, synaptophysin can be demonstrated in a range of neural and neuroendocrine tissues, 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.

X-linked intellectual disability

Mutations in this gene have been implicated in X-linked intellectual disability.

Interactions

Synaptophysin has been shown to interact with AP1G1 and SIAH2.

References

References

1. "Entrez Gene: SYP synaptophysin".
2. (November 1987). "The cDNA and derived amino acid sequences for rat and human synaptophysin". Nucleic Acids Research.
3. (May 1996). "Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release". Proceedings of the National Academy of Sciences of the United States of America.
4. (August 2009). "Detection of behavioral alterations and learning deficits in mice lacking synaptophysin". Neuroscience.
5. (December 1996). "Comparative evaluation of synaptophysin-based methods for quantification of synapses". Journal of Neurocytology.
6. (May 1986). "Synaptophysin: a marker protein for neuroendocrine cells and neoplasms.". Proceedings of the National Academy of Sciences of the United States of America.
7. (2003). "Manual of Diagnostic Cytology". Greenwich Medical Media, Ltd..
8. (May 2009). "A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation". Nature Genetics.
9. (November 2002). "Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin". Molecular and Cellular Neurosciences.
10. (March 2002). "Regulation of synaptophysin degradation by mammalian homologues of seven in absentia". Journal of Biological Chemistry.