This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: The cells of higher organisms such as mammals, flies and fungi enclose their genetic material in a nucleus. A nuclear envelope, consisting of two stacked membranes, protects it.
For the cell to survive, the nucleus must constantly exchange molecules with the rest of the cell. This exchange relies on channels called nuclear pores, which act as selective gates that transport proteins or messenger RNA in or out. Before this pore complex can be assembled, the cell must first punch an opening through both membranes and then seamlessly seal the edges.
How cells accomplish this was a long-standing puzzle. Now, research teams at the Institute of Biochemistry, led by ETH professors Ulrike Kutay, Karsten Weis and Madhav Jagannathan, together with colleagues from the University of Fribourg and other partners, have solved the puzzle. Their findings not only answer a fundamental question in cell biology but also offer an explanation and a potential therapeutic approach for a hereditary form of dystonia, a rare but severe movement disorder.
The corresponding studies have been published in the journal Molecular Cell. The researchers have shown for the first time that two tools are required for the envelope's two membranes to fuse perfectly: the enzyme Torsin-1A and a complex of several CLCC1 units (in humans) or their fungal counterparts, Brl1 and Brr6. Until now, it was known that a defect in Torsin-1A halts nuclear pore assembly—with fatal consequences for the cell.
The researchers show how this cooperation works: Torsin-1A binds to CLCC1 and helps several of these building blocks join together. Torsin-1A then accompanies the CLCC1 complex to the site of pore assembly to enable membrane fusion. The exact mechanism of the fusion also caught the research teams by surprise.
Using computer simulations, they hypothesized that CLCC1 proteins (or their relatives Brl1 and Brr6 in fungi) forge a temporary channel inside the nuclear envelope. This allows fat molecules (lipids) to flow across the bilayers, rendering the local membrane unstable and forcing the fusion of the two nuclear membranes. "We had not expected such a mechanism," explains the first author of one of the studies, Daria Maslennikova, who completed her doctorate in Kutay's group.
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