What Determines Kinesin Direction of Movement?

Within every living cell, a transportation network exists, ensuring that vital materials reach their destinations. At the heart of this system are molecular motor proteins known as kinesins. These proteins function as microscopic engines, moving along cellular highways to transport various cargo, including organelles and vesicles filled with signaling molecules. The directed movement of kinesins is fundamental to a cell’s organization, allowing it to function, grow, and communicate.

Microtubules: The Kinesin Roadway

The tracks for this intracellular transport system are microtubules, which are long, hollow cylinders constructed from a protein called tubulin. These microtubules form a dynamic network stretching throughout the cell’s interior. They are not static structures but can rapidly assemble and disassemble, allowing the cell to remodel its internal architecture as needed.

A defining feature of these microtubule tracks is their inherent polarity. Each microtubule has two distinct ends, a “plus-end” and a “minus-end,” which arises from the way tubulin proteins add to the growing structure. In most animal cells, the minus-ends of microtubules are anchored at a central location called the centrosome, near the cell’s nucleus. From this central hub, microtubules extend outwards with their plus-ends reaching towards the periphery of the cell, establishing a clear directional framework.

How Kinesins Walk: The Engine of Movement

Kinesins move along these polarized microtubule tracks using a mechanical process powered by chemical energy from adenosine triphosphate (ATP). As enzymes called ATPases, they can break down ATP to release the energy stored in its chemical bonds. This energy release drives the physical changes in the kinesin protein that result in forward motion.

The movement is described as a “walking” or “hand-over-hand” motion. A kinesin protein has two globular “head” domains connected to a stalk that attaches to the cargo. In a stepwise cycle, one head binds firmly to the microtubule. The breakdown of an ATP molecule on this bound head causes a flexible region called the neck linker to swing the second head forward. The second head then binds to a new site further along the microtubule as the trailing head detaches, allowing the kinesin to move processively without falling off.

Navigating the Cell: Kinesin Directionality

The direction a kinesin takes is determined by its molecular structure. Most kinesin families are plus-end directed motors, meaning they walk towards the plus-end of the microtubule. This transports cargo from the cell’s interior towards its periphery. This directionality is dictated by the architecture of the motor domain—the “head” region—and its interaction with the flexible neck linker, which propels the other head forward in a specific direction.

However, not all kinesins follow this rule. An exception is the kinesin-14 family, which moves in the opposite direction, toward the microtubule’s minus-end. These proteins have their motor domain located at a different end of the protein chain than most plus-end directed kinesins, and this structural difference determines their reversed movement. Furthermore, some kinesins, like those in the kinesin-5 family, are specialized not for cargo transport but for sliding microtubules against each other.

Cellular Roles Dictated by Direction

The direction of kinesin movement is directly linked to its function within the cell. The plus-end directed movement of most kinesins is responsible for anterograde transport, moving materials away from the cell center. In nerve cells, kinesins transport vesicles containing neurotransmitters down the long axon to the synapse. This process also delivers mitochondria to areas of high energy demand and brings building blocks for growth and repair to the cell’s edge.

Conversely, minus-end directed transport is important for cellular maintenance. This movement, known as retrograde transport, is carried out by kinesin-14 and a different class of motor proteins called dyneins. It allows the cell to bring materials back from the periphery to the center for recycling or degradation. During cell division, the directional control of different kinesins becomes paramount, as kinesin-5 motors push microtubules apart to form the mitotic spindle while minus-end directed kinesins pull chromosomes towards the newly forming daughter cells, ensuring each receives a complete set of genetic material.