Human SNX7 blocking peptide

Sorting nexin (SNX) family proteins are best characterized for their abilities to regulate protein trafficking during processes such as endocytosis of membrane receptors, endosomal sorting, and protein degradation, but their in vivo functions remain largely unknown. We started to investigate the biological functions of SNXs using the zebrafish model. In this study, we demonstrated that SNX7 was essential for embryonic liver development. Hepatoblasts were specified normally, and the proliferation of these cells was not affected when SNX7 was knocked down by gene-specific morpholinos; however, they underwent massive apoptosis during the early budding stage. SNX7 mainly regulated the survival of cells in the embryonic liver and did not affect the viability of cells in other endoderm-derived organs. We further demonstrated that down-regulation of SNX7 by short interfering RNAs induced apoptosis in cell culture. At the molecular level, the cellular FLICE-like inhibitory protein (c-FLIP)/caspase 8 pathway was activated when SNX7 was down-regulated. Furthermore, overexpression of c-FLIPS was able to rescue the SNX7 knockdown-induced liver defect. Conclusion: SNX7 is a liver-enriched antiapoptotic protein that is indispensable for the survival of hepatoblasts during zebrafish early embryogenesis. (HEPATOLOGY 2012;55:19851993)

We have updated the clinical description of a large Scottish pedigree, in which patients were affected by spastic paraplegia complicated by hearing impairment and persistent vomiting due to hiatal hernia inherited as an autosomal dominant trait. Using a genome-wide mapping approach, we identified a novel locus (SPG29) for this form of hereditary spastic paraplegia on chromosome 1p31.1-21.1 and narrowed it to 22.3cM between markers D1S2889 and D1S248. Sequencing of one candidate gene in the region (sorting nexin 7, SNX7 involved in several stages of intracellular trafficking and protein transport, showed no disease-causing mutations.