Topic
STX5
About: STX5 is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 15 citations. The topic is also known as: SED5 & STX5A.
Papers
TL;DR: It is postulated that Stx5 can directly bind to the C-terminal domain of VLDL-R, thereby influencing the receptor's glycosylation, trafficking and processing characteristics, and might play a role in modulating VLDl-R physiology by participating in an abrasively described or completely novel Golgi-bypass pathway.
17 citations
TL;DR: This is the first time a mutation in an alternative starting codon is linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.
Abstract: The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identified a novel human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Whereas Golgi morphology was unaltered, primary human dermal fibroblasts isolated from these patients showed defective glycosylation and mislocalization of glycosyltransferases. Measurements of anterograde trafficking, based on biotin-synchronizable forms of Stx5 (the RUSH system), and of cognate binding SNAREs, based on Forster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. This is the first time a mutation in an alternative starting codon is linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.
TL;DR: In this article, the authors identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform.
Abstract: The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Forster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2020 | 1 |
| 2013 | 1 |