HGNC Approved Gene Symbol: SYNGR1
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38): 22:39,349,991-39,385,575 (from NCBI)
Rat synaptogyrin, or RATSYNGR1, is an integral membrane protein associated with presynaptic vesicles in neuronal cells. See SYNGR2 (603926). As part of an effort to sequence the long arm of human chromosome 22, Kedra et al. (1998) identified the human homolog of RATSYNGR1, synaptogyrin-1 (SYNGR1). By a combination of EST database searching and library screening, the authors isolated cDNAs corresponding to 3 alternatively spliced transcripts, which they designated SYNGR1a-c. The predicted 1a, 1b, and 1c proteins contain 234, 191, and 192 amino acids, respectively. Northern blot analysis revealed that the 4.5-kb SYNGR1a mRNA is expressed at high levels in brain. The other transcript forms are expressed at low levels in nonneuronal tissues. In situ hybridization to embryonic and adult mouse tissues confirmed that SYNGR1a, the most abundant transcript form, shows predominantly neuronal expression. Kedra et al. (1998) also identified cDNAs encoding the related human proteins SYNGR2 and SYNGR3 (603927) and mouse Syngr1b. Like RATSYNGR1, the mouse and human synaptogyrin family members contain 4 membrane-spanning domains. The conserved central portion of SYNGR1a shares 54%, 61%, and 92% identity with that of SYNGR2, SYNGR3, and RATSYNGR1, respectively.
Kedra et al. (1998) determined that the SYNGR1 gene contains 6 exons.
By inclusion within mapped clones, Kedra et al. (1998) mapped the SYNGR1 gene to chromosome 22q13. These authors found that SYNGR2 is located on 17qter and noted that the synaptogyrins and several other gene families contain paralogous genes located on chromosomes 17 and 22. They stated that this result supports the hypothesis that 17q and 22q are evolutionarily closely related, and that these 2 regions in the human genome are the result of a large chromosome duplication.
Using gene targeting, Janz et al. (1999) generated mice lacking Syngr1. They bred these Syngr1 knockout mice against Syp (313475) knockout mice generated by McMahon et al. (1996) to create double knockout mice deficient in both Syp and Syngr1. Both single and double knockout mice were viable and fertile. Morphologic and biochemical analysis showed that the architecture and composition of synapses were unaltered in the brains of Syngr1 single knockout and Syngr1/Syp double knockout mutant mice. Electrophysiologic recordings in the hippocampal CA1 region revealed that short- and long-term synaptic plasticity was severely reduced in the Syngr1/Syp double knockout mice without changes in the fundamental release apparatus, vesicle cycling, or release probability. Janz et al. (1999) concluded that Syngr1 and Syp perform essential and redundant functions in synaptic plasticity without being required for synaptic transmission as such.
From the results of cotransfection experiments, Janz et al. (1999) concluded that Syp and Syngr1 are phosphorylated by c-fyn and c-src tyrosine kinases. The absence of Syp and Syngr1 in knockout mice did not markedly affect tyrosine phosphorylation of other proteins.
Janz, R., Sudhof, T. C., Hammer, R. E., Unni, V., Siegelbaum, S. A., Bolshakov, V. Y. Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 24: 687-700, 1999. [PubMed: 10595519] [Full Text: https://doi.org/10.1016/s0896-6273(00)81122-8]
Kedra, D., Pan, H.-Q., Seroussi, E., Fransson, I., Guilbaud, C., Collins, J. E., Dunham, I., Blennow, E., Roe, B. A., Piehl, F., Dumanski, J. P. Characterization of the human synaptogyrin gene family. Hum. Genet. 103: 131-141, 1998. [PubMed: 9760194] [Full Text: https://doi.org/10.1007/s004390050795]
McMahon, H. T., Bolshakov, V. Y., Janz, R., Hammer, R. E., Siegelbaum, S. A., Sudhof, T. C. Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release. Proc. Nat. Acad. Sci. 93: 4760-4764, 1996. [PubMed: 8643476] [Full Text: https://doi.org/10.1073/pnas.93.10.4760]