Mitotic cell divisions, long thought to produce two identical daughter cells, are not entirely equal, according to a new
study published this week in
Proceedings of the National Academy of Sciences. Proteins destined for degradation are preferentially inherited by one cell over the other, the researchers found.
"We hit on an observation that people had missed for 100 years," said
Eddy De Robertis of the University of California, Los Angeles, who led the study.
Chromosomes and the mitotic machinery are usually partitioned equally into each new daughter cell during mitosis. Researchers generally assumed this was also true of all other cellular material. But De Robertis and his colleagues now show that for spent proteins, cell division yields an uneven split -- even when dividing cells are bound for the same
cell fate.
De Robertis' team focused on a cell signaling protein called Smad1. After Smad1 is activated, it becomes primed for destruction through a series of phosphorylation events. The researchers used antibodies specific to phosphorylated Smad1 and found that 80-90% of dividing human embryonic stem cells shared the protein unequally. Smad1 proteins when not phosphorylated, however, were entirely uniform.
Asymmetric mitoses were also observed in two other phosphorylated proteins primed for destruction, and in two other cell types: monkey cells
in vitro, and
Drosophila embryos
in vivo. What's more, the researchers showed that unequal distributions were maintained through three consecutive cell divisions.
De Robertis hypothesizes that that when centrosomes -- a main component of the
microtubule organizing center -- duplicate and separate to occupy opposite poles of the dividing cell, the material surrounding the centrosomes remains largely in one pole. Such imbalance may act as a cleansing mechanism to keep one daughter cell "pristine," while the other cell undergoes apoptosis, he said.
Yukiko Yamashita of the University of Michigan, Ann Arbor, however, was not convinced that asymmetrical mitoses are necessarily an adaptive cellular clean-up process. An alternative scenario, she told
The Scientist, is that some centrosomes build more microtubules than others. These microtubules then attract more organelles, which results in proteasomes and their target proteins becoming unequally distributed.
To test whether "bad" proteins are indeed confined into one cell to protect the other,
Yamashita proposed disrupting the asymmetric segregation of proteins destined for degradation to see whether it leads to premature cell
aging and senescence.