By: Hayden Lim Khai Eun
Introduction
Right now, your brain is doing something extraordinary. Not just the usual magic of keeping you alive while you skim this article, but something far more intricate: it’s storing these very words as memories.
In less than twenty minutes, a flurry of protein synthesis will ignite within your neurons, solidifying this experience into a lasting trace. How does your brain pull this off? It turns out the answer lies in a fascinating process called dendritic translation, and we got one of the most jaw-dropping tools yet to study it — TurboID.
What is TurboID?
To put it simply, TurboID is a revolutionary platform capable of capturing the molecular choreography that happens in dendrites, those spindly extensions of neurons that receive signals at synapses. This process is central to learning and memory, and it’s so complex it would make even the most seasoned researchers feel like they’re still in Biology 101. But thanks to TurboID, we’re finally getting answers to questions that have puzzled neuroscientists for decades.
What’s more, TurboID is such a cool name, and it really does give this tool justice, especially considering its wide range of applications and its immense importance in the neuroscience field, as discussed later.
Dendritic Translation
To really fathom TurboID’s impact, let’s dive into the mechanics. When you learn something new—whether it’s a fact, a skill, or just an unforgettable punchline—your neurons don’t just passively store that information. They work actively to modify their synapses, strengthening or weakening connections in a process called synaptic plasticity.
Here’s where dendritic translation comes in. As Rockefeller’s Robert B. Darnell puts it, the inner workings of dendritic translation a “holy grail for understanding memory formation”, emphasising the very importance of understanding dendritic translation.
Unlike other cells, neurons often need to produce proteins locally, right at the synapse. Why? Because time is of the essence. Sending materials all the way from the cell body to distant dendrites would take too long for something as dynamic as memory formation.
Instead, neurons keep messenger RNAs (mRNAs) stockpiled in their dendrites, ready to be translated into proteins when needed. This localized protein synthesis is the molecular equivalent of having a pop-up factory right where the demand is highest.
However, studying this process has always been a technical nightmare. The molecular machinery at synapses operates on such a fine scale that traditional methods felt like trying to listen to a symphony with earmuffs on. TurboID changed that.
How TurboID works
TurboID is basically a biochemical labeling system that works like a precision tracker for protein synthesis. Developed by a team at Rockefeller University, including Robert Darnell and Ezgi Hacisuleyman, it uses a specially engineered enzyme that tags nearby proteins with biotin - a molecular “sticky note.” Once tagged, these proteins can be isolated and studied with remarkable clarity.
The absolute beauty of TurboID is its speed and spatial precision. Unlike older techniques that required hours or even days to generate results, TurboID operates in minutes, capturing the molecular events happening in dendrites as they unfold (essentially, it’s like swapping a Polaroid camera for a high-speed DSLR).
When the team applied TurboID to study dendritic translation, the results were nothing short of astonishing. They discovered that when neurons are activated—say, during a learning experience—local ribosomes latch onto mRNAs and begin producing proteins.
And, they didn’t just find the usual suspects of protein synthesis. They uncovered a whole new class of tiny proteins called… micropeptides. Yes, you read that right, micropeptides, even smaller versions of proteins. And you thought AP Biology was already confusing enough.
Micropeptides (Small but Mighty)
These tiny proteins, previously overlooked in the cellular landscape, appear to play a critical role in the synaptic changes that underpin memory. TurboID revealed that neurons produce over 1,000 distinct micropeptides in response to activation. What do they do? That’s still an open question, but their sheer abundance suggests they’re anything but trivial.
One hypothesis is that micropeptides act as molecular modulators, fine-tuning the synaptic environment to optimize plasticity. Another idea is that they serve as scaffolds, helping larger proteins assemble into functional complexes. Either way, their discovery opens a new frontier in neuroscience, one that could redefine our understanding of how memories are formed and stored.
The team also identified a critical RNA-binding protein called FMRP, already known to be involved in synaptic function and associated with Fragile X syndrome. TurboID showed that FMRP is essential for the ribosome-mRNA interaction that drives micropeptide production. Without FMRP, the entire system grinds to a halt, leading to disruptions in protein synthesis that may underlie cognitive deficits seen in Fragile X and other intellectual disabilities.
Applications of TurboID
The implications of TurboID extend far beyond the lab. Since it is capable of providing a detailed map of the molecular machinery involved in dendritic translation, it helps to pave the way for targeted therapies for neurological disorders, potentially impacting millions, if not billions of people around the globe.
Imagine treatments that could restore proper protein synthesis in conditions like Alzheimer’s disease, autism, or epilepsy. Imagine understanding how stress or trauma alters synaptic protein production—and finding ways to reverse those changes. Imagine, imagine, imagine… Just imagine!
Disadvantages
Unsurprisingly, just like every scientific invention out there, while TurboID is a groundbreaking tool in neuroscience, no technology is without its limitations. For one, TurboID uses a biotin ligase enzyme to label nearby proteins rapidly, as mentioned earlier. While this is a notable strength in capturing real-time protein interactions, its high reactivity can also carry the risk of labelling off-target proteins. In other words, picture a student strong in mathematics speeding through a test paper. Without checking his answers again, he is bound to make careless mistakes. Similarly, without proper equipment to help check the accuracy of TurboID, its strength may become its weakness.Specifically, this nonspecific labeling can generate background noise, making it harder to distinguish meaningful and relevant data.
On top of that, another key disadvantage is that TurboID introduces enzymes and biotin into cellular environments. In certain contexts, this can overload the system, potentially altering normal cellular functions. For example, an overabundance of biotin can interfere with native biotin-dependent processes, creating artifacts in the data. This poses threats to not only the data, but also to these important biological processes, especially if it's conducted in a living organism (which brings me to my last point).
Lastly, while TurboID works exceptionally well in cultured neurons, applying it in live animals poses logistical challenges, thus posing a doubt to the viability and the potential of TurboID to address neurological diseases in the first place.
Conclusion
Science is often a slow, methodical march toward understanding, but every so often, a discovery like TurboID accelerates the pace. And we need to be thankful for that.
As Robert Darnell nicely put it, “When you develop a new technique like TurboID, it’s like walking into a dark room and flipping on the light. Suddenly, you can see everything, and it’s breathtaking.”
TurboID not only has a cool name, but it also plays an important role in how we understand the brain. Who knows? Maybe this may just open the floodgate for more such inventions or even lay the foundation for the treatment of complex neurological diseases.
TurboID has just given us a priceless new year’s wish, that may soon turn into reality.
On behalf of everyone at Neurohub, here’s wishing you a happy new year!
References
“Intriguing Science Discoveries of 2024 - News.” News, 23 Dec. 2024, www.rockefeller.edu/news/36948-intriguing-science-discoveries-of-2024/.
Cho, Kelvin F., et al. “Proximity Labeling in Mammalian Cells with TurboID and Split-TurboID.” Nature Protocols, vol. 15, no. 12, 2 Nov. 2020, pp. 3971–3999, https://doi.org/10.1038/s41596-020-0399-0.
Creative Proteomics. “TurboID Service 2 - Creative Proteomics.” Creative-Proteomics.com, 2018, www.creative-proteomics.com/services/turboid-service-2.htm.
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