Stx5-Mediated ER-Golgi Transport in Mammals and Yeast
CELLS
Authors: Linders, Peter T. A.; van der Horst, Chiel; ter Beest, Martin; van den Bogaart, Geert
Abstract
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 5 (Stx5) in mammals and its ortholog Sed5p in Saccharomyces cerevisiae mediate anterograde and retrograde endoplasmic reticulum (ER)-Golgi trafficking. Stx5 and Sed5p are structurally highly conserved and are both regulated by interactions with other ER-Golgi SNARE proteins, the Sec1/Munc18-like protein Scfd1/Sly1p and the membrane tethering complexes COG, p115, and GM130. Despite these similarities, yeast Sed5p and mammalian Stx5 are differently recruited to COPII-coated vesicles, and Stx5 interacts with the microtubular cytoskeleton, whereas Sed5p does not. In this review, we argue that these different Stx5 interactions contribute to structural differences in ER-Golgi transport between mammalian and yeast cells. Insight into the function of Stx5 is important given its essential role in the secretory pathway of eukaryotic cells and its involvement in infections and neurodegenerative diseases.
Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics
CELL REPORTS
Authors: Iacoangeli, Alfredo; Lin, Tian; Al Khleifat, Ahmad; Jones, Ashley R.; Opie-Martin, Sarah; Coleman, Jonathan R., I; Shatunov, Aleksey; Sproviero, William; Williams, Kelly L.; Garton, Fleur; Restuadi, Restuadi; Henders, Anjali K.; Mather, Karen A.; Needham, Merilee; Mathers, Susan; Nicholson, Garth A.; Rowe, Dominic B.; Henderson, Robert; McCombe, Pamela A.; Pamphlett, Roger; Blair, Ian P.; Schultz, David; Sachdev, Perminder S.; Newhouse, Stephen J.; Proitsi, Petroula; Fogh, Isabella; Ngo, Shyuan T.; Dobson, Richard J. B.; Wray, Naomi R.; Steyn, Frederik J.; Al-Chalabi, Ammar
Abstract
We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 x 10(-9)), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: 2.1 +/- 1.3 kg/A allele, p = 0.053; rs3828599: 1.0 +/- 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.
COA
Publication 
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