9.A.34 The Nuclear Pore Complex Biogenesis (NPC-B) Family 

Three proteins have been implicated in nuclear export in yeast.  These proteins are the Brl1 protein, a nuclear export system protein (Saitoh et al. 2005), the Brr6 protein of a similar function (de Bruyn Kops and Guthrie 2001), and Apq12 which forms a complex with Brl1 and Brr6 (Lone et al. 2015).  They collectively seem to function in lipid homeostasis and maintenance of the nuclear envelop.  Brr6 is reported to be required for mRNA nuclear export. It may also be involved in nuclear pore complex (NPC) distribution and nuclear envelope morphology (de Bruyn Kops and Guthrie 2001).
 
A protein known to localize to and be important in the assembly of both the yeast NPC and the spindle pole body, which functions as the microtubule organizing center, is the 6 TMS protein, Ndc1p (NPC1 in humans (see TC# 1.I.1). The N- and C-termini of Ndc1p are exposed to the cytoplasm (Lau et al. 2006). The paralogous Brr6 and Brl1 are conserved integral membrane proteins of the nuclear envelope (NE) (see TC# 9.A.34). Depletion of Brr6 and Brl1 caused defects in NPC biogenesis, whereas the already assembled NPCs remained unaffected. This NPC biogenesis defect was not accompanied by a change in lipid composition, but Brl1 interacted with Ndc1 and Nup188 as well as transmembrane and outer and inner ring NPC components, indicating a direct role in NPC biogenesis.Both Brr6 and Brl1 associate with a subpopulation of NPCs and emerging NPC assembly sites. BRL1 overexpression affected NE morphology and suppressed the nuclear pore biogenesis defects of Δnup116 and Δgle2 cells. Possibly Brr6 and Brl1 transiently associate with NPC assembly sites where they promote NPC biogenesis (Zhang et al. 2018).