Membrane fusion is a critical process in supporting various cellular activities. Most of the studies have focused on the heterotypic membrane fusion, such as SNARE mediated vesicular membrane fusion. But little is known about the homotypic membrane fusion which connects organelles including the endoplasmic reticulum (ER) and mitochondria.

Dysfunction of ER membrane fusion leads to hereditary spastic paraplegia in human. HU Junjie from Institute of Biophysics (IBP) of Chinese Academy of Sciences and other scientists has identified a class of membrane-bound dynamin-like GTPases named atlastin (ATL) that meditates ER homotypic membrane fusion. But not all eukaryotic organisms express ATL. Another family of GTPases, like Sey1p in yeast and RHD3 in plant, was found to be functional ortholog of ATL. However, Sey1p and RHD3 are much longer than ATL, and have different distribution along ER membranes, indicating a different mechanism.

In a recent study entitled "Structures of the Yeast Dynamin-like GTPase Sey1p Provide Insight into Homotypic ER Fusion" published on The Journal of Cell Biology, Prof. RAO Zihe’s and HU Junjie’s groups from IBP illustrated the molecular mechanism of homotypic membrane fusion mediated by yeast ER fusogen Sey1p. This study presented an unidentified configuration of the dynamin superfamily, and compared the fusion process of Sey1p and ATL.

Prof. RAO Zihe’s group determined the structures of candida albicans Sey1p with different GTP analogues. HU Junjie’s group tested Sey1p functions using biochemical and cell biology assays, and found that Sey1p and ATL have similar membrane fusion steps but the power stroke of fusion reaction occurs at different stages. Sey1p can mediate fusion without GTP hydrolysis, even though fusion is much more efficient with GTP. In addition, the punctate localization of Sey1p is dependent on its GTPase activity.

This study deepens people’s understanding of how membrane fusion is achieved. Because of Dr. HU Junjie’s contribution to the field of ER membrane fusion, he was interviewed by the “People & Ideas” of The Journal of Cell Biology recently.

Figure: Models for fusion mediated by Sey1p and ATL. The structures of Sey1p determined in this study were shown on left. The structures of ATL reported previously were shown on right for comparison. (Image by HU Junjie's Group)