Synapsin I

File:PBB Protein SYN1 image.jpg

Synapsin I Protein

Synapsin I, is the collective name for Synapsin Ia and Synapsin Ib, two nearly identical phosphoprotiens. 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. 706 amino acids comprise Synapsin Ia and the same 670 amino acids starting from the N-terminal comprise Synapsin Ib.

Function

Synapsin I is found in the nerve terminal of axons, specifically in the membranes of synaptic vesicles based on immunocytochemistry. This phophoprotein is as an endogenous substrate bound to the vesicular membrane. It is phosphorylated by several protein kinases including those activated by cAMP and calcium/calmodulin. The tail portion of the protein, the C-terminal end, bears two phosphorylation sites at which calcium/calmodulin dependent protein kinase acts, and the N-terminal globular domain contains the cAMP dependent protein kinase mediated phosphorylation site.

Characterization

Both Synapsin I proteins are highly based with a pI in the range of 10.2 and 10.3. Synapsin I is found in two isoforms, Synapsin Ia and Ib and makes up approximately 6% of the total protein in synaptic vesicles. Among bovine, rat, and human it has been shown to be 95% homologous, with the central 'C' domain evolutionarily conserved. This phosphoprotein is loosely associated with the vesicular membrance and is easily dissociated by treatment with a salt, versus a detergent being required for its removal from the membrane.

Structure

The phosphoprotein is made up of a globular portion at the N-terminal and an elongated C-terminal domain, rendering it a largely elongated protein on the whole. Rich in the amino acids prorine and glycine, the compositional and structural natures of this protein are somewhat similar to collagen. This aided in the early determination of its structure using collagenase, and which was later confirmed confirmed by amino acid sequencing and modern techniques. Cleavage of Synapsin I by collaganase fragments the elongated C-terminal and leaves the globular N-terminal domain intact.

History

The first member of the synapsin family, Synapsin I was discovered, purified, and initial characterized by Tetsufumi Ueda and Nobel Prize winnerPaul Greengard in 1977, at Yale University. Orignally named Protein I, it was found as an endogenous substrate for cAMP dependent protein kinase in the synaptic membrane of the rat brain and was the first collganeous protein to be described in the nervous system. The amino acid sequencing was determined subsequently by Thomas Sudorf and colleagues.

Gene

The human gene for this protein is known as SYN1.

Further References

Krueger, B., Forne,X., and Greengard, P. (1977). "Depolarization-induced phosphorylation of specific proteins, mediated by calcium ion influx, in rat brain synaptosomes". J. of Biological Chemistry: 2764–2773. PMID 323254. {{cite journal}}: Unknown parameter |Volume= ignored (|volume= suggested) (help)CS1 maint: multiple names: authors list (link)

Ueda, T. and Greengard, P. (1977–1978). "Unpublished findings". Original Manuscript.{{cite journal}}: CS1 maint: date format (link) CS1 maint: multiple names: authors list (link)

Schulman, H. and Greengard, P. (1978). "Stimulation of brain membrane protein phosphorylation by calcium and an endogenous heat-stable protein". Nature: 478–479. PMID 628428. {{cite journal}}: Unknown parameter |Volume= ignored (|volume= suggested) (help)CS1 maint: multiple names: authors list (link)

Greengard, P. (1978). Cyclic Nucleotides, Phosphorylated Proteins, and Neuronal Function. Raven Press, New York. p. 124. ISBN 0890042810.