SNARE proteins help the dynamin-like GTPase atlastin to fuse ER membranes together, Lee et al. reveal.
ER tubules fuse with each other to form an interconnected network that spreads throughout the cytoplasm. Homotypic ER fusion is mainly mediated by the atlastin family of dynamin-like GTPases, although, in the absence of the yeast atlastin Sey1p, SNARE proteins, which promote various membrane fusion events in the cell, can support a residual amount of ER membrane fusion. Whether SNARE proteins usually function in atlastin-mediated ER fusion is unclear, however.
Lee et al. developed an in vitro assay to measure the Sey1p-dependent fusion of purified ER membranes and found that fusion was reduced when ER-localized SNAREs, such as Sec22p, were inhibited. Moreover, Sey1p bound to ER SNARE complexes, suggesting that the two protein families work together to promote ER membrane fusion.
Sey1p can stimulate the fusion of artificial liposomes on its own, but Lee et al. discovered that this was only true when Sey1p was present at a much higher level than its physiological concentration. In vivo, Sey1p may rely on SNAREs for efficient fusion, a requirement that might prevent ER tubules from mistakenly fusing with all the other organelles they contact in the cell.
Lee et al. found that, in vitro, Sey1p acts before SNAREs during ER fusion. Senior author Youngsoo Jun now wants to investigate whether Sey1p’s main role is to tether ER membranes close enough together for SNAREs to drive their fusion.
Text by Ben Short