The effect of removing a component from the nuclear pore complex
Removing a single component from the large nuclear pore complex has surprising effects during cell differentiation
Highlights:
Scientists from Max Planck Institute of Biophysics, Université Paris Cité and Heidelberg University studied the nuclear pore complex in mouse cells.
Research conducted on mouse embryonic stem cells revealed that without Nup133, nuclear pores form abnormally and lead to issues in neuron development.
The absence of Nup133 resulted in large openings in the nuclear envelope of neural progenitor cells, indicating potential disintegration of nuclear pores.
Text: Stefanie Boehm, Reiya Taniguchi, Pamela Ornelas
The main task of the nucleus is to keep the eukaryotic cell’s genetic material safe. It is surrounded by a protective barrier called the nuclear envelope, which can protect it from harmful invaders and other types of damage. Small openings in the nuclear envelope, called nuclear pores, control the molecular transport in and out of the nucleus, allowing a selective exchange of necessary materials with the remaining cell. Now, Reiya Taniguchi and coworkers, in collaboration with the lab of Valerie Doye and Hans-Georg Kräusslich, have found that nuclear pores are more than a permeability barrier, as they also protect the nucleus from mechanical stress.
Nuclear pores are large complexes made of hundreds of individual pieces arranged as three stacked rings, with an eightfold symmetry. This structure is conserved across many different species. One key element of these complexes is Nup133, which could appear to be necessary to shape their ring-like structure. At first sight, one could expect that removing a crucial building block from the assembly would cause the entire structure to collapse. Surprisingly however, this is not the case with Nup133. Scientists have seen that even when Nup133 is missing, most nuclear pores remain undamaged, while only certain cells at specific developmental stages are affected by its absence.
In this study, published in the journal Nature Cell Biology, the researchers investigated mouse embryonic stem cells without Nup133. They found that without it, their nuclear pores form in a structurally heterogenous fashion. Using a new computational approach, they were able to study the structure of individual nuclear pores directly in cells at a high resolution. In contrast to the known highly conserved architecture of the nuclear pore, those lacking Nup133 showed abnormal symmetries and missing components. Although the stem cells showed no obvious differences against their counterparts, they failed to develop into neurons. The authors further compared the nuclear pore structure in stem and neural progenitor cells with and without Nup133, and found large openings in the nuclear envelope of the Nup133 deficient progenitor cells. These openings did contain bits and pieces of nuclear pore complexes, suggesting that these holes are sites where nuclear pores might have disintegrated.
During differentiation of stems cell to their mature specialized form, such as neurons, the shape of the nucleus changes and mechanical forces put pressure on the nuclear envelope. Reiya and coworkers propose that an unperturbed nuclear pore arrangement, including Nup133, for example, helps protect the nuclear envelope under situations with additional stress. In the presented model, the nuclear pore acts like a spring that allows the nuclear pore to stretch to a larger diameter, relieving tension on the remaining nuclear envelope. In cases where the nuclear pore complex is not intact or if the mechanical strain is too high, the complex disintegrates, potentially causing the envelope to rupture and compromising its essential protective barrier function.
