RIMS2 blocking peptide

The cytomatrix active zone (CAZ) is a specialized cellular structure regulating release of vesicles. We reported previously increased expression of three CAZ genes, piccolo, RIMS2 and RIMS3 in the amygdala in schizophrenia. This study determined the levels of gene and protein expression for components of the active zone including two additional CAZ genes in the amygdala from subjects with schizophrenia and non-psychiatric controls, as well as the effects of antipsychotic drugs. Whilst relative real-time PCR analysis did not identify significant change in the expression of six additional active zone genes, Western blot analysis showed increased piccolo and RIMS2 protein expression in the amygdala in schizophrenia. In vitro analysis suggests antipsychotic drug treatment was unlikely to have caused the changes in RIMS2, RIMS3 and piccolo expression observed in the amygdala in schizophrenia. Therefore, this study provides further evidence suggesting that piccolo, RIMS2, RIMS3, but not the entire components of the active zone are involved in the neurobiology of schizophrenia. (c) 2008 Elsevier Ltd. All rights reserved.

Background Non-synonymous mutations altering tumor suppressor genes and oncogenes are widely studied. However, synonymous mutations, which do not alter the protein sequence, are rarely investigated in melanoma genome studies. Methods We explored the role of somatic synonymous mutations in melanoma samples from TCGA (The Cancer Genome Atlas). The pathogenic synonymous mutation and neutral synonymous mutation data were used to assess the significance of pathogenic synonymous mutations in melanoma likely to affect genetic regulatory elements using Fisher's exact test. Poisson distribution probabilities of each gene were used to mine the genes with multiple potential functional synonymous mutations affecting regulatory elements. Results Concentrating on five types of genetic regulatory functions, we found that the mutational patterns of pathogenic synonymous mutations are mostly involved in exonic splicing regulators in near-splicing sites or inside DNase I hypersensitivity sites or non-optimal codon. Moreover, the sites of miRNA binding alteration exhibit a significantly lower rate of evolution than other sites. Finally, 12 genes were hit by recurrent potentially functional synonymous mutations, which showed statistical significance in the pathogenic mutations. Among them, nine genes (DNAH5, ADCY8, GRIN2A, KSR2, TECTA, RIMS2, XKR6, MYH1, SCN10A) have been reported to be mutated in melanoma, and other three genes (SLC9A2, CASR, SLC8A3) have a great potential to impact melanoma. Conclusion These findings confirm the functional consequences of somatic synonymous mutations in melanoma, emphasizing the significance of research in future studies.