The human body’s tiny antennae keep life in tune – powered by a hidden motor

In each of the human body’s billions of cells, a tiny antenna stands guard – a cilium – attuned to the body’s signals and keeping the machinery of life in sync.

But when the cilium can no longer clean itself, the conversation falters. The rhythm breaks, and then the path can lead to blindness, kidney failure or disruption of the metabolic balance.

“This shows that cilia are constantly fine-tuning their contents – as if they first lose control and then try to regain balance,” explains Lotte Bang Pedersen, Professor of Cell Biology at the University of Copenhagen, Denmark.

The motor protein KIF13B appears to play a key role in this by deciding whether proteins get recycled or expelled in small or large vesicles. The discovery uncovers a previously unknown layer of the cell’s cleaning machinery – the subtle mechanics that keep the human body’s internal communication clear and precise.

“Cilia are found on almost every cell in the human body, and for a long time, we thought of them as extras – until it turned out they were running the show,” says Lotte Bang Pedersen.

“Most people know the motile cilia – the ones in our airways that sweep away dust and mucus so that we can breathe freely. But almost all other cells have a different kind: a single, non-motile extension that works like an antenna. Until about 2000, we thought that they did not really do anything – but in just 25 years, that view has completely changed.”

She compares the cilium to a sensitive antenna – and to a filter that must stay clean to receive signals.

“If it gets clogged, the cell loses its ability to detect what its surroundings are telling it,” she adds.

From overlooked to indispensable – the antenna is reborn

Just a few decades ago, non-motile cilia were almost forgotten. Today, they have been promoted to the role of signal managers.

“When I came to Yale University in the early 2000s,” she says, “the non-motile cilia were still something of a mystery. We honestly thought that they did not do anything special – until everything changed. Suddenly it became clear that these tiny structures could control how organs are formed – and how they function,” remembers Lotte Bang Pedersen.

Cilia act as the human body’s sensory and signalling stations – registering and responding to everything from growth cues to fluid flow.

“The non-motile cilia are now known to be central to how the human body regulates development, growth and communication between cells,” she says.

When the cell’s antenna controls its own circuit

Cilia consist of an internal skeleton surrounded by a membrane studded with specialised receptors that detect impulses such as growth factors, fluid flow or hormonal signals. When a signal is received, the receptor must be swiftly removed or recycled – otherwise the signal keeps firing and can damage the cell.

“The cilium functions both as an antenna and as a control centre,” notes Lotte Bang Pedersen. “It is both a sensor and a sorting station – it has to stay clean to sense properly, but it also uses energy to expel excess molecules.”

When the cilium’s cleaning system fails, it can lead to diseases such as kidney failure, blindness and metabolic disorders – collectively known as ciliopathies.

Then came an unexpected twist: the cilia themselves send out messages in tiny bubbles – extracellular vesicles. Clean-up? Yes. But perhaps also active communication.

“This is still a relatively new field,” explains Lotte Bang Pedersen. “We know that if the cilium cannot remove its receptors through the usual transport routes, it starts cutting off small vesicles instead. But we still do not know whether this is merely waste disposal – or whether these vesicles also act as messengers.”

This question is propelling the whole field forward.

When the cell’s antenna cleans up its own signals

To understand how cilia maintain their health and control their protein balance, the researchers grew kidney cells in which the KIF13B gene had been knocked out and compared them with normal cells.

“We combined advanced imaging with mass spectrometry – a technique that can measure thousands of proteins at once,” says Lotte Bang Pedersen. “This enabled us to determine what was happening inside the cells and, at the same time, measure which signalling molecules were changing.”

Over several days, the researchers found how the absence of the KIF13B protein gradually shifted the balance between small and large vesicles.

“Early in the process, certain signalling proteins accumulate in the cilia,” she says. “But over time, the same proteins start appearing in large vesicles outside – as if the cell changes strategy along the way.”

To determine exactly which proteins were being released, the team isolated both the small and large vesicles and analysed their contents using mass spectrometry, which demanded extreme precision and patience.

“It was like looking for a needle in a haystack,” she adds with a smile. “The number of ciliary vesicles is extremely low, so we had to purify the samples again and again until the patterns became clear.”

Five attempts – and the secret of the motor becomes visible

The work was carried out in collaboration with two laboratories in Germany – at Johannes Gutenberg University of Mainz and the University of Tübingen – which specialise in mass spectrometry and statistical data analysis, ensuring that the observed differences were real and not just background noise.

“We ended up running the experiments five times independently to be sure,” she says. “When we found the same changes again and again, we could be fairly confident that KIF13B acts as a kind of traffic regulator – a protein that decides when signal molecules should be retrieved and when they should be released.”

By combining imaging, biochemistry and quantitative data, the researchers connected what they found – accumulation and release – with specific changes in protein composition.

In short, the missing motor revealed the choreography that keeps the cell’s rhythm in tune.

The motor that keeps the cell’s rhythm

The researchers clearly found that KIF13B acts as a gatekeeper at the base of the cilium.

When the motor protein is missing, the balance breaks down: signalling proteins that would normally be removed promptly start to build up inside the cilia until the cell eventually responds with an emergency clean-up.

“When KIF13B is missing, the cell cannot retrieve its signalling proteins,” explains Lotte Bang Pedersen. “They become trapped in the cilium and put pressure on the system. After a while, the cell tries to restore balance by pushing the load out in large vesicles.”

The process unfolds in two acts: first, pressure builds – then comes the release. A dramatic shift from fine-tuning to rough clean-up.

In the beginning, certain signalling proteins accumulate inside the cilia, but as the system collapses, the same proteins start appearing in large vesicles outside the cell.

When the rhythm breaks down, the cell loses control

The analysis revealed that the large vesicles from cells lacking KIF13B were filled with molecules that normally belong inside the cilium – proteins that control both signalling and structure. In addition, the smaller vesicles were missing several of the proteins that keep the length and stability of cilia in check.

“This is essentially how the cell switches signals on and off in time and space,” explains Lotte Bang Pedersen. “The cilia decide which receptors are to be active – and remove them again once the signal has been delivered. When the motor disappears, the sorting breaks down and the cell starts to send out the wrong messages.”

Even the physical structures showed changes. Under an electron microscope, the researchers saw tiny bumps on the surface of the cilia – small bulges seemingly ready to release their load. These bumps became far more frequent when KIF13B was knocked out.

“This fits perfectly with our model,” she says. “The cilia form small blisters along their sides and release them – as if the cell is trying to save itself from drowning in its own signals.”

Taken together, the results show that the KIF13B protein functions not only as a motor but also as a key actor in cilium self-regulation – the finely tuned balance that keeps the internal environment stable.

Without KIF13B, the cilium begins to leak its contents: regulatory proteins escape into large vesicles, and the smaller ones lose their building blocks. Sorting breaks down, and communication between cells becomes distorted.

The fingerprint that reveals the health of the cell

The discovery that KIF13B regulates the protein content of cilia fundamentally changes understanding of how cells maintain the health of their sensory organelles.

Earlier research had focused mainly on how cilia detect signals, but Lotte Bang Pedersen and colleagues now show that they also clean themselves and fine-tune their signalling machinery over time.

“Cilia are not just recipients,” notes Lotte Bang Pedersen. “They take an active role. They switch off once a signal has been delivered – and get rid of the used parts. This system almost seems to think for itself.”

This insight could have far-reaching implications for understanding of both development and disease.

“We can begin to read the health of the cilia in the vesicles they release – a kind of molecular fingerprint,” she explains. “If we learn to interpret it, we may be able to use these vesicles as biomarkers – a new way to diagnose and monitor disease.”

When the clean-up fails – and the body loses its balance

When the cilia’s cleaning system breaks down, the cell loses its grip on growth, communication and energy metabolism – the very forces that normally keep the human body in balance. When they fail, the result can be diseases such as kidney failure, obesity and diabetes.

Two new proteins – CCDC92 and CCDC198 – emerged unexpectedly in the vesicles released by the cells. When the genes for these proteins are knocked out in mice, the animals develop symptoms similar to ciliopathies.

“This was one of the big surprises,” says Lotte Bang Pedersen. “Mice with these genes knocked out have symptoms resembling ciliopathies. We believe that they could be new candidates for diseases we do not yet fully understand.”

The research group is now collaborating with clinicians and geneticists in the European consortium Therapies for Renal Ciliopathies, which is developing treatments for hereditary kidney disorders. “Pinpointing the exact gene behind a disease is rarely easy,” she explains. “But if we know that it is linked to defective cilia or vesicles, finding the answer becomes much easier.”

For Lotte Bang Pedersen, the perspective extends far beyond the boundaries of diagnosing disease. Researchers focus not only on microscopic structures but also on the deeper principle of maintaining order amid complexity – which both cells and human societies depend on.

“Ultimately, it is about listening,” she concludes quietly. “When the cell stops cleaning up, it loses its connection to the world – just as the human body loses its balance.”