Finding Your Way Through a Crowded Cell

The cell is a densely populated community. It is also a fast-paced metropolis where macromolecular complexes and membrane-enclosed organelles can move swiftly along cytoskeletal highways. A seismic shift in our understanding of how a living cell is organized was brought on some 30 years ago by the discovery of green fluorescent protein (GFP), which allowed scientists to study the behavior of proteins and organelles in real time and in their natural environment. It showed us that proteins confined to endosomal membranes—such as the immune receptor major histocompatibility complex (MHC) class II—move bidirectionally along microtubules, rather than following unidirectional trajectories. This development raised questions regarding how this choreographed movement is regulated and the purpose it may serve. (Remember, it’s crowded on and around the cellular highways!) Over the years, we and others have identified many regulators of endosomal transport, including RILP and FYCO1, the effectors of the small GTPase Rab7, which bind to the dynein/dynactin and kinesin motors, respectively.