An essential nuclear envelope integral membrane protein, Brr6p, required for nuclear transport

Despite rapid advances in our understanding of the function of the nuclear pore complex in nuclear transport, little is known about the role the nucle ar envelope itself may play in this critical process. A small number of int egral membrane proteins specific to the envelope have been identified in bu dding yeast, however, none has been reported to affect transport. We have i dentified an essential gene, BRR6, whose product, Brr6p, behaves like a nuc lear envelope integral membrane protein. Notably, the brr6-1 mutant specifi cally affects transport of mRNA and a protein reporter containing a nuclear export signal. In addition, Brr6p depletion alters nucleoporin distributio n and nuclear envelope morphology, suggesting that the protein is required for the spatial organization of nuclear pores. BRR6 interacts genetically w ith a subset of nucleoporins, and Brr6-green fluorescent protein (GFP) loca lizes in a punctate nuclear rim pattern, suggesting location at or near the nuclear pore. However, Brr6-GFP fails to redistribute in a Delta nup133 mu tant, distinguishing Brr6p from known proteins of the pore membrane domain. We hypothesize that Brr6p is located adjacent to the nuclear pore and inte racts functionally with the pore and transport machinery.