Tubulin-VDAC Interaction: Salt Dependence of Conductance and Reversal Potential

Abstract

The recently reported blocking of mitochondrial voltage-dependent anion channel (VDAC) by tubulin [1] has raised new questions about the role of tubulin C terminal tails (CTT) in the low conductance states exhibited by VDAC channel. The voltage sensitive reversible channel closure observed suggests that tubulin is more than an enhancer of VDAC gating. However, there is no conclusive evidence about the nature of the channel interaction with tubulin tails. Experiments have also revealed that VDAC-tubulin interaction is also influenced by the lipid composition of the membrane hosting the channel. While the duration of tubulin induced closure seems to be independent of salt concentration, the opposite is true with VDAC open time between successive blockages. The change in conductance between open and close states is also concentration dependent. By performing single channel conductance measurements as well as reversal potential measurements (in open and closed states) we analyze the importance of electrostatic interactions between VDAC ionizable residues and the CTT negative charge in the binding of tubulin. The anion selectivity of VDAC in its open state is turned into cation selectivity under tubulin blockage. The recently published 3D structure of VDAC [2] seems fully compatible with the partial penetration of alpha or beta tubulin tails into the channel lumen.[1] T. K. Rostovtseva et al. PNAS, 105 (2008) 18746.[2] S. Hiller et al. Trends Biochem. Sci., 35 (2010) 514.