Modulation of Membrane Rigidity by Sar1, a Vesicle Trafficking Protein

Abstract

Intracellular cargo trafficking involves dramatic changes in membrane shape, the mechanics of which remain poorly understood. We focus on Sar1, the key regulator of the coat protein complex II (COPII) family that ferries newly synthesized proteins from the endoplasmic reticulum (ER), and the only member of the COPII coat that interacts directly with the ER lipid bilayer membrane. To investigate whether Sar1 has a role beyond merely localizing the other COPII proteins, we directly measure the force involved in membrane deformation as a function of its concentration, using optically trapped microspheres to pull tethers from in vitro lipid membranes whose composition and large surface area mimic the composition and geometry of the ER. We find that Sar1 lowers the rigidity (bending modulus) of lipid membranes to nearly zero in a concentration-dependent manner. Moreover, Sar1 lacking its N-terminal amphipathic helix induces negative (concave) spontaneous membrane curvature. These results reveal a paradigm-altering insight into COPII trafficking: Sar1 actively alters the material properties of the membranes it binds to, lowering the energetic cost of curvature generation.View Large Image | View Hi-Res Image | Download PowerPoint Slide