Barriers to export

Nuclear pores facilitate transport into and out of the nucleus. But now Roth et al. report that cells with more of the nucleoporin DNup88 do less nuclear export (page 701). DNup88 exerts this negative effect by sequestering the exportin DCRM1 so that it can no longer do its job.

Roth et al. first established that cells with DNup88 were compromised for nuclear export but not import. The overactive export in cells lacking DNup88 could be prevented by inhibiting DCRM1, which shuttles its cargos out of the nucleus. DNup88, DCRM1, and the nucleoporin DNup214 are normally found in a complex on the cytoplasmic face of the nuclear pore, but loss of DNup88 frees up DCRM1 so that it can enter the nucleus and help export more proteins.

The authors found a correlation between DNup88 levels and the effectiveness of nuclear export at different stages of fly development. Such alterations of DNup88 levels may be one way of altering the rates of export of many substrates, rather than tweaking the binding of individual substrates to DCRM1 by, for example, phosphorylation. But Roth et al. are also on the lookout for phosphorylations or other modifications of the DNup88/DCRM1 system that may alter export capability in response to specific signals. ▪