Israeli and US scientists have made a significant discovery regarding the mechanisms that govern molecular movement in and out of human cell nuclei. This breakthrough may provide insights into diseases such as cancer, Alzheimer”s, and ALS.
The research team, comprising experts from Hebrew University of Jerusalem, the Quantitative Biosciences Institute at the University of California, San Francisco, The Rockefeller University, and Albert Einstein College of Medicine, focused on nuclear pore complexes (NPCs). These microscopic structures are essential for controlling cellular traffic, allowing specific molecules to enter or exit the nucleus.
Dr. Barak Raveh, the study”s lead author, described the team”s innovative model as functioning like a “virtual microscope,” enabling them to visualize the rapid operations of these tiny gateways. “By integrating numerous independent experiments and utilizing computer simulations, we can observe the functionality of this gate in real-time,” he explained.
Raveh likened NPCs to advanced security checkpoints. Each complex, despite its diminutive size, can permit millions of molecules to pass every minute while meticulously excluding unwanted substances. This selectivity has baffled scientists for decades, particularly because the small dimensions of NPCs make direct observation challenging.
Previous theoretical models proposed that NPCs functioned through rigid gates or sponge-like sieves, failing to clarify how these structures could allow large molecules through while remaining highly selective. The new study combines empirical data with computational modeling to reveal the dynamics at play at the molecular level.
Within the NPCs exists a densely packed network of protein chains known as FG repeats. These continuously moving chains create an environment that obstructs unaccompanied molecules but allows smaller ones to traverse. Larger molecules can pass through if they are escorted by nuclear transport receptors—molecular “passports” that transiently interact with the FG chains to facilitate their movement.
Professor Michael Rout from The Rockefeller University noted, “The transport process resembles a dynamic dance on a bridge, where only those with the correct partners—the receptors—can cross. Molecules lacking these escorts are turned away.” This model resolves a long-standing question about how NPCs can permit large molecular complexes to pass while still keeping smaller entities out.
Professor Andrej Sali of QBI at UCSF stated, “Our findings offer the first clear explanation for the remarkable selectivity of NPCs.” He further emphasized the potential this research holds for advancements in medicine and biotechnology.
Professor David Cowburn from Albert Einstein College of Medicine highlighted the immediate relevance of these findings for understanding disorders associated with faulty nuclear transport, including ALS, Alzheimer”s, and various cancers.
This discovery also opens avenues for practical applications. Researchers might leverage this knowledge to develop drugs that can manipulate molecular traffic within cells or engineer synthetic nanopores that mimic the functions of NPCs, facilitating targeted delivery of treatments to the nucleus. Such innovations could enhance laboratory techniques and tools designed for high-precision molecular analysis.
The study”s findings have been published in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS).
