MEMBRANE CHOLESTEROL IS A NOVEL CONTROL FOR KINESIN-BASED TRANSPORT*

Motor protein-based transport in cells underlies all eukaryotic cell function and survival; dysfunctions in this transport are implicated in many diseases, including neurodegeneration. While the properties of motor proteins have been extensively studied both in vivo and in vitro, many important questions remain, including how the properties of the cargo itself impact motor function. In cells, cargos are often membrane-bound; the composition of the cargo membrane has long been hypothesized to impact motor protein-based transport. Here we combined advances in membrane biophysics with single-molecule optical-trap experiments to characterize the transport of membrane-enclosed cargos in vitro. We found that coupling motors via a biomimetic membrane significantly enhanced the transport of cargos along tau-decorated microtubules. This effect diminished when we added cholesterol to our model membrane. To our knowledge, our study uncovers the first direct link between cargo-membrane composition and kinesin function. The experimental approach employed here is generally applicable as a controlled experimental platform for interrogating the control of motor proteins in a context directly relevant to in vivo scenarios.