Along the microtubules, one locomotive can help another

Far from being vast oceans where molecules drift at will, our cells are organized into different functional regions. Cytoskeletal proteins constitute both the framework and the transport pathways between one site and another. In neurons, for example, neurotransmitters synthesized in the cell body are transported, aboard vesicles, to the end of the axon, where they are released into the synaptic cleft (the space between two neurons) during the propagation of the nerve signal. A molecular motor, kinesin, actively transports these vesicles along cytoskeletal filaments, the microtubules. Transport is oriented: kinesin circulates on the microtubules from the "minus" end, positioned near the cell nucleus, to the "plus" end, which points toward the periphery. On the return journey, another motor protein carries cargo from the periphery to the nucleus: dynein.

Although the ability of these two molecular locomotives to move along the microtubule "rails" has long been known, some of their properties still perplex biologists. Among other things, certain cargoes can be bound simultaneously to both locomotives and yet move smoothly from one end of a microtubule to the other. Imagine the vesicle as a captive balloon, pulled by two locomotives traveling in opposite directions. Shouldn't the vesicle then find itself in a tug-of-war, and therefore sometimes be blocked, sometimes progressing jerkily in one direction and then the other? Even more intriguing: when the cell is deprived of one of the two engines, all traffic is impeded, not just one direction of travel.

These findings suggest that the two vesicle-bound motors are not operating at the same time, but that kinesin and dynein nevertheless cooperate for transport in both directions. To identify the molecular mechanisms of this cooperation, British researchers reconstituted in vitro the molecular structures formed between kinesin, dynein and an adaptor protein, HOOK3, which ensures the docking of the motors to their cargo. On the one hand, they detailed their three-dimensional structure using cryo-electron microscopy and, on the other hand, by identifying them using fluorescent labels, they followed their movement along microtubules polymerized on the surface of glass slides using microscopy.

You have 33.26% of this article left to read. The rest is reserved for subscribers.