Transmembrane proteins shaping lipid bilayers: Curvature-induced sorting and diffusion

Patricia Bassereau .

Abstract:
The targeting of transmembrane proteins to specific cellular regions is essential for proper cell function. Extensive work has been done to identify specific protein/protein interactions, specific motives, active processes governing protein targeting as well as the contribution of hydrophobic mismatch. However, membranes such as transport intermediates, the dendrites of neurons or primary cilia can be highly curved, with curvature radii of tens of nanometers. Thus, the matching of protein shape to the underlying membrane curvature may also provide a targeting mechanism that was not demonstrated yet.
We have used a quantitative in-vitro assay based on membrane nanotube pulled from giant liposomes (GUVs) to demonstrate that membrane curvature can strongly affect the lateral distribution of transmembrane proteins. For this, we have studied two proteins: a voltage-gated potassium channel (KvAP) with a conical shape and Aquaporin 0 (AQP0) with a cylindrical shape.
I will next present a systematic study of the effect of tube radius on the lateral diffusion coefficient of KvAP, using single particle tracking of quantum dots attached to the proteins. We find that diffusion is reduced in tubular membranes when tube radius narrows. Eventually, I will show that KvAP and AQP0, although they have the same lateral size, have different diffusion coefficients on a quasi-flat membrane when its tension is lowered, in apparent contradiction with Saffman-Delbrück’s theory.