Interactions between the amino acids in the proteins CRM1 (magenta) and the human form of RanGTP (green). Image credit: Li et al. (CC BY 4.0)
Plant, animal and fungal cells all store their DNA inside the cell’s nucleus. Small molecules can freely cross the membrane that surrounds the nucleus, but pores in the membrane control when larger molecules enter or leave. This transport process is an essential part of healthy cell behavior.
To leave the nucleus, large molecules need to carry a coded sequence called a nuclear export signal. In yeast cells, which are often used to study cell biology, this sequence allows cargo to bind to a groove in so-called molecular cargo vehicles, such as a protein called CRM1. A protein called RanGTP binds to CRM1 to supply the energy needed to transport molecules across the membrane. Outside of the nucleus, another protein called RanBP1 closes up the groove in the CRM1 protein to help remove the cargo by interacting with RanGTP and CRM1 to form a ‘complex’.
The version of RanBP1 found in animal cells has its own nuclear export signal, which led researchers to question whether it works in the same way as yeast RanBP1. To find out, Li et al. compared yeast RanBP1 with mouse RanBP1. This revealed that mouse RanBP1 lacks the amino acids that allow it to interact with CRM1 in the fashion of yeast RanBP1. When unloading cargo from CRM1, mouse RanBP1 does not form a complex with Ran and CRM1; instead, it works entirely through removing RanGTP from CRM1. This process is more efficient than the one used by yeast cells, but it uses twice as much energy.
The results presented by Li et al. demonstrate that even processes that are essential to cells can be optimized to fit the needs of different species. Future work could potentially exploit the differences in the export processes used by fungi and animal cells to develop new anti-fungal treatments.
