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.
Highlights
The secretory pathway is essential for secretion of cytokines, hormones, growth factors, and extracellular matrix proteins, as well as for the delivery of receptors and transporters to the cell membrane and lytic proteins to endo-lysosomal compartments
The different binding of Sed5p/syntaxin 5 (Stx5) to Sec24 might relate to differences in COPII function among yeast and mammals
COPII mediates anterograde trafficking from the endoplasmic reticulum (ER) directly to the cis-Golgi [7], whereas in mammals, COPII vesicles fuse together to form the ER-Golgi intermediate compartment (ERGIC) [2,4]
Summary
The secretory pathway is essential for secretion of cytokines, hormones, growth factors, and extracellular matrix proteins, as well as for the delivery of receptors and transporters to the cell membrane and lytic proteins to endo-lysosomal compartments. Exocytic and endocytic SNAREs are often functionally redundant, and knockout or knockdown mostly has no or a very minor phenotype [9] This is different for Stx5/Sed5p and other ER-Golgi SNAREs, which have been shown in in vitro studies to be highly stringent with purified Sed5p only being able to form a SNARE complex with other SNAREs involved in Golgi-ER trafficking Gos1p (Qb), Bos1p (Qb), Sft1p (Qc), Bet1p (Qc), Ykt6p (R), and Sec22p (R) [41,42]. Rate-limiting for the transit of chylomicrons through the enterocyte is the exit of chylomicrons from the ER to the cis-Golgi in specialized 250 nm-sized transport vesicles This process involves a t-SNARE complex of Stx, Vti1a, and Bet and the v-SNARE VAMP7, which, based on inhibition of these SNAREs with antibodies, is believed to mediate the fusion of the chylomicrons with the cis-Golgi [48]. This has never been studied side-by-side with the same assays, and whether the dual function as Bet as both a t- and v-SNARE is true remains to be established
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