Just how a dividing cell rebuilds the nuclear envelope, the protective, functional wrapping that encases both the original and newly copied genetic material, has been a source of controversy for the last 20 years.
The answer matters because the architecture established during formation of the envelope is regarded as key to future regulation of gene expression.
Now scientists at the Salk Institute of Biological Studies, reporting in the September 9 advanced online edition of Nature Cell Biology, lay the debate to rest. Studying frog eggs, they discovered that the endoplasmic reticulum (ER), a key cellular organelle shaped like a network of tubes, flattens part of itself during mitosis to form a double-sided sheet, which then bends around what will become the nucleus, the control hub of the cell.
“The process is simple and elegant,” says Martin W. Hetzer, Ph.D., an assistant professor in the Molecular and Cell Biology Laboratory, who explains, “the membrane tubules are flattened as they associate with chromatin. Our model does not involve vesicle fusion.”
The most dramatic event during nuclear assembly following replication and separation of chromosomes is the reformation of the nuclear envelope, a highly structured barrier that separates the nuclear interior from the rest of the cell, say Hetzer and Daniel J. Anderson, a graduate student in Hetzer's lab and co-author of the study. The envelope is the gateway into the nucleus and, thus, restricts access to the genome; it is composed of a concentric double membrane that is penetrated by nuclear pores, which serve as transport channels between the nucleus and the cytoplasm.
Just as chromosomes duplicate, the cell's organelles, including the ER, also reproduce themselves. “The ER is always there and remains an intact network of tubes,” says Hetzer. In a mature cell the ER works closely with the genome, synthesizing and transporting the proteins produced under the direction of genes housed inside the nucleus.
Some scientists have believed that the ER in the sister cells help form the nuclear envelope, although proof of the process has been lacking. Others have argued that the new membrane is resurrected from bits of the “old” nuclear membrane that disintegrates when nuclear chromosomes duplicate and pull apart during mitosis. “The problem with this theory, however, is that these fragments would then have to be fused together in the newly produced cells, and that would require massive membrane fusion and a dedicated protein machinery,” Hetzer says. “But no one has ever found it. Our data suggests that the search for this fusion machinery is now obsolete,” he says.