Disease relevance of SYN3

• No association between synapsin III gene promoter polymorphisms and multiple sclerosis in German patients [1].
• We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha (Ad-IFNalpha) together with the gene transfer-enhancing agent Syn3 [2].

High impact information on SYN3

• The human synapsin III gene is located on chromosome 22q12-13, which has been identified as a possible schizophrenia susceptibility locus [3].
• Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32 [4].
• This level of genome complexity is far greater than that described previously for the synapsin I and II genes and suggests that synapsin III may have functions distinct from those described for synapsins I and II [5].
• To follow the transport of human syntaxin (Syn) 3 to the apical surface of intestinal cells, we produced and expressed in Caco-2 cells a chimera made of the entire Syn3 coding sequence and the extracellular domain of the human transferrin receptor (TfR) [6].
• Association of the SYN3 variations and haplotypes with MS is not evident in German MS patients - in contrast to a MS cohort from Italy, as reported previously [1].

Biological context of SYN3

• BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia [4].
• The findings support a role for synapsin III in a subset of African American patients with schizophrenia and raises questions about selective pressure in Africa to account for the extraordinary disparity of the 469 and 470 single-nucleotide polymorphisms in different ethnic populations [7].
• We investigated whether the polymorphisms rs133946 and rs133945 in the promoter region of the synapsin III (SYN3) gene are associated with multiple sclerosis in German patients [1].
• The synapsin III gene is located on human chromosome 22q12-q13, where a possible schizophrenia susceptibility locus is located [8].
• Using the single strand conformation polymorphism method, we searched for variants in 13 exons and the 5'-flanking region of the synapsin III gene in schizophrenia [8].

Anatomical context of SYN3

• The observed stronger regulation of synapsin III might be due to still active neurite elongation and a rather early state of presynaptic maturation at the time-point investigated, as synapsin III was previously found to be highly enriched in growth cones and during early synaptic development [9].
• The gene coding for synapsin III, an intrinsic synaptic vesicle membrane protein, maps to this target region [7].
• To test the potential role of Syn3 in apical transport, we overexpressed it in Caco-2 cells and measured the efficiency of apical and basolateral delivery of several endogenous markers [6].

Other interactions of SYN3

• Synapsin III is a new synapsin family gene with the putative function of synaptogenesis regulation and neurotransmitter release in the brain [10].
• In contrast, the SYN 3 and GPC 1 expression showed a continuous decline from ED 14 to ED 24 [11].
• The F line had higher SYN 2 (ED 14, 18, 20, 22), SYN 3 (ED 22), and SYN 4 (ED 22) expression than the RBC2 line [11].
• Examples of interesting candidates are AKAP6 for arrythmogenic right ventricular dysplasia 3 and SYN3 for familial partial epilepsy with variable foci [12].
• Distinct genes encode the three different isolated proteins (I, II and III); of interest, the gene of synapsin III (SYN3) is located in the chromosome 22q12-q13, a locus close to one of the candidate susceptibility regions (22q13.1) for MS [13].

Analytical, diagnostic and therapeutic context of SYN3

• We mapped synapsin III to chromosomal region 22q13 (13.1-13.31) by fluorescence in situ hybridization, a region that has been identified as a potential schizophrenia susceptibility locus [14].

References