Sar1-GTP induces membrane curvature and tubule formation.


COPII vesicles form from the endoplasmic reticulum (ER). Now, Marcus Lee, Randy Schekman (University of California, Berkeley), and Lelio Orci (University of Geneva, Switzerland) find that insertion of the amphipathic α helix of the Sar1 GTPase causes membrane deformation that initiates, and eventually ends, this vesicle formation process.

The group investigated how COPII coats shape the ER by examining in isolation how each set of COPII proteins—Sar1, Sec23/24, and Sec13/31—influences membrane curvature.

When activated Sar1-GTP was incubated with spherical liposomes, the researchers saw that the spheres strikingly developed long, narrow tubules ∼26 nm in diameter. They then determined that insertion of Sar1's α helix into the lipid bilayer is responsible for this transformation. “When you stick an object into 1 of 2 layers in a bilayer, you cause membrane deformation that results in extra surface tension. The most favorable way to relieve this tension is by forming tubules,” Schekman explains.

The group also found that Sec23/24 could bend membranes. Rather than inserting a protein domain into the lipid bilayer, this complex forms a concave, bowtie-shaped dimer that presumably presses the membrane against its underbelly to create membrane curvature. Sec23/24 dimers likely become organized into a lattice by the Sec13/31 scaffolding complex to ultimately form vesicles 70 nm in diameter. Schekman's and Orci's groups think that Sar1 initiates membrane deformation, and then Sec23/24 recruitment “captures” the bent membranes to better mold the curvature, with help from Sec13/31 for cargo containment.

Although Sec23/24 and Sec13/31 complexes could create budded vesicles on spherical liposomes, the buds rarely closed off to form free vesicles when the Sar1 helix was absent. “This is an unexpected finding,” says Schekman. “We think that the curvature induced by Sar1 is necessary at this point to press the neck of the vesicle together to complete the fission process.”


Lee, M.C., et al.