Details

Autor(en) / Beteiligte

• Liu, Tina Yu
• Bian, Xin
• Sun, Sha
• Hu, Xiaoyu
• Klemm, Robin W
• Prinz, William A
• Rapoport, Tom A
• Hu, Junjie

Titel

The role of the C‐terminus and transmembrane segments in facilitating atlastin‐mediated endoplasmic reticulum fusion

Ist Teil von

• The FASEB journal, 2013-04, Vol.27 (S1)

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract only Generation of the tubular endoplasmic reticulum (ER) network requires homotypic membrane fusion. This is mediated in metazoans by atlastin (ATL), a dynamin‐like GTPase that consists of an N‐terminal cytosolic domain followed by two transmembrane segments (TMs) and a C‐terminal tail (CT). A GTP‐hydrolysis‐induced conformational change in the N‐terminal cytosolic domain is required for fusion, but it is unclear if this alone is sufficient for the fusion reaction. Here, we show using in vitro fusion assays that the CT and TMs are required for efficient fusion. A conserved amphipathic helix in the CT promotes fusion by interacting with and perturbing the lipid bilayer. The TMs not only serve as membrane anchors but also mediate ATL oligomerization. Point mutations in the CT or the TMs also impair ATL's ability to maintain ER membrane morphology in vivo . Our results suggest that protein‐lipid and protein‐protein interactions in the membrane cooperate with the conformational change of the cytosolic domain to achieve fusion and maintain the tubular ER network. These findings are relevant to mechanisms used by other membrane fusion proteins, such as mitofusins/Fzo1p, viral fusogens, and SNAREs.