The cell has to turn it on and off, exactly when needed.
Deep within every nerve cell, a molecular machine called kinesin-1 walks ceaselessly along protein tracks, delivering the cargo that keeps neurons alive — and when it fails, the consequences are devastating. Researchers at UC Davis have now, for the first time, seen the precise shape of this machine in its dormant state, revealing how the cell locks and unlocks it with molecular precision. Published in July 2026, the discovery illuminates not only a forty-year mystery of cellular biology, but also the broken switches behind incurable diseases like ALS — and with that clarity comes, at last, a door worth opening.
- Mutations in kinesin-1 have long condemned patients to ALS, Charcot-Marie-Tooth Disease, and hereditary spastic paraplegia — paralysis, blindness, and pain with no cure in sight.
- The central puzzle — how a cell turns its own molecular motor on and off — resisted scientists for four decades, because the mechanism was invisible until now.
- Using cryo-electron microscopy, UC Davis researchers finally captured kinesin-1 frozen in its off state: folded in half like a locked broomstick, its legs immobilized and its cargo port sealed shut.
- The activating protein MAP7 acts as a molecular crowbar, wedging into the folded structure and releasing it — a discovery that reframes how scientists understand cellular motor control.
- With the lock now visible, researchers can begin designing drugs to repair the broken switches behind neurodegenerative disease — a long road, but one with a map for the first time.
Inside every nerve cell lives a molecular machine shaped like a broomstick with stubby legs. This protein, kinesin-1, walks along internal tracks at one hundred steps per second, hauling neurotransmitters and vital cargo from the cell's center to its outermost branches. Without it, cargo never arrives, cells sicken, and neurons die.
For forty years, scientists understood how kinesin-1 walks — each step powered by splitting a molecule of ATP — but the question of how cells turn it on and off remained unanswered. Molecular biologists Jawdat Al-Bassam and Richard McKenney at UC Davis suspected the answer was hidden in the protein's dormant shape. Using cryo-electron microscopy, their team — led by postdoctoral researcher Md Ashaduzzaman — finally saw it: the broomstick folded in half, its top end wedged between its own legs, held rigid by a connector acting like a rubber band. Legs locked. Cargo port sealed. Machine paralyzed.
The activating protein MAP7, it turns out, functions as a molecular crowbar — latching onto the folded structure, popping the rubber band loose, and allowing the broomstick to unfold and spring to life. Published in Science Advances on July 15, 2026, Al-Bassam described the finding as "the pinnacle of understanding how cells can turn on motors, precisely, to go to different places at different times."
The stakes reach far beyond basic science. Mutations in kinesin-1 cause ALS, Charcot-Marie-Tooth Disease Type 2, and hereditary spastic paraplegia — conditions marked by paralysis, cognitive decline, blindness, and pain, all currently incurable. Many of these mutations break the very on-off switch now revealed. With the structure finally visible, researchers can begin imagining drugs that might correct the defect — repairing the lock rather than simply watching it fail. The path from discovery to treatment remains long, but for the first time, scientists can see exactly what they are trying to fix.
Inside every nerve cell lives a molecular machine that never stops working. It is a protein shaped like a broomstick—tall, skinny, with stubby legs—and its job is to walk. Step after step, at a pace of one hundred steps per second, it travels along tracks made of other proteins, hauling packages of neurotransmitters and vital cargo from the cell's center outward to the tips of branches that reach toward thousands of neighboring cells. Without this protein, called kinesin-1, a nerve cell cannot function. The cargo never arrives. The cell sickens. The cell dies.
For forty years, scientists have understood how kinesin-1 walks—each step powered by breaking apart a molecule called ATP, like a tiny explosion that propels the protein forward. But they faced a puzzle that no one could solve: How does the cell turn this machine on and off? The protein has no brain, no judgment. Left to its own devices, it would walk forever, or not at all. The cell must control it with precision, activating it only when cargo needs to move, only when the moment is right.
Jawdat Al-Bassam and Richard McKenney, molecular biologists at UC Davis, suspected the answer lay in the protein's shape when it was dormant. They knew that a protein called MAP7 somehow switched kinesin-1 on, but the mechanics remained hidden. In 2026, using a technique called cryo-electron microscopy—taking thousands of photographs of frozen protein and stitching them together into a three-dimensional image—Al-Bassam's team, led by postdoctoral researcher Md Ashaduzzaman, finally saw what the turned-off protein looked like. The broomstick was folded in half. Its top end was wedged between its own legs, locked in place by a connector that acted like a rubber band, holding the whole structure rigid. The legs could not move. The cargo attachment site was blocked. The machine was paralyzed.
When MAP7 arrives and latches onto the protein's back, it wedges into the folded structure and pops the rubber band loose. The broomstick unfolds. The legs spring free. The cargo site opens. The machine comes alive. The discovery, published in Science Advances on July 15, 2026, represents what Al-Bassam called "the pinnacle of understanding how cells can turn on motors, precisely, to go to different places at different times."
The implications extend far beyond basic science. Mutations in the kinesin-1 gene cause diseases that have no cure: amyotrophic lateral sclerosis, or ALS, which paralyzes the body while the mind remains trapped inside; Charcot-Marie-Tooth Disease Type 2, which destroys the nerves that control movement and sensation; and hereditary spastic paraplegia 10, which causes progressive paralysis, cognitive decline, blindness, and relentless pain. Many of these mutations work by breaking the on-off switch—preventing the cell from controlling its broomstick. Now that researchers can see exactly how the switch works, they can begin to imagine how a drug might repair it. "It might be possible to design a molecule that would bind the mutant protein and correct its defect," Al-Bassam said. McKenney added that having these clear structures "will be a major advance" for drug design, opening "a lot of new scientific questions." The work was funded by the National Institutes of Health and conducted at UC Davis's Biological Electron Microscopy Campus Core, with collaborators from Johns Hopkins University. The path from structure to treatment remains long, but for the first time, researchers can see the lock they need to pick.
Notable Quotes
This is the pinnacle of understanding how cells can turn on motors, precisely, to go to different places at different times.— Jawdat Al-Bassam, UC Davis associate professor of molecular and cellular biology
If you want to design drugs, having these clear structures will be a major advance for that. This will open up a lot of new scientific questions.— Richard McKenney, UC Davis professor of molecular and cellular biology
The Hearth Conversation Another angle on the story
Why does it matter that we can now see the folded shape? Couldn't scientists have guessed at it?
Guessing and seeing are different things. For forty years, people had theories. But when you actually see the rubber band holding the legs in place, when you see exactly where MAP7 wedges in to release it—that's when you can start designing something to fix it when it breaks.
So mutations in kinesin-1 are causing these diseases right now, in people alive today?
Yes. ALS, Charcot-Marie-Tooth, hereditary spastic paraplegia—some of these are genetic. A person inherits a broken version of the gene, the protein misfolds or won't respond to MAP7, and their nerve cells start dying. There's no treatment.
How long until a drug based on this discovery could actually help someone?
That's honest uncertainty. The structure is the foundation. Drug design comes next. Testing. Clinical trials. Years, probably. But without seeing the lock, you can't even begin to design the key.
The protein walks at one hundred steps per second. That's fast.
Incredibly fast. And it has to be. A nerve cell can be a meter long. The cargo has to get there. If the protein moved slowly, the neurotransmitters would degrade before they arrived.
What happens when kinesin-1 fails?
The cargo piles up at the center of the cell. The branches starve. The cell can't communicate with its neighbors. Eventually the nerve cell dies. In ALS, this happens to the motor neurons that control your muscles. You lose the ability to move, to speak, to swallow.
Is this discovery going to lead directly to a cure?
It's a necessary step, not a guarantee. But it's the first time we've actually understood the mechanism well enough to think about fixing it. That's different from where we were yesterday.