page 915, Cronshaw et al. now describe a proteomic analysis of mammalian NPCs that arrives at a surprising tally of mammalian nucleoporins: 29. Despite the numerical similarity, the new work identifies important differences between the two systems and establishes a basis for comparison.
The authors obtained a highly purified NPC fraction from rat liver, and then used mass spectrometry to identify and characterize the proteins making up the NPC. Although the NPCs appear to have remained intact through the purification, only 29 nucleoporins were identified in the final preparation. Two-thirds of the nucleoporins are conserved between yeast and mammalian NPCs, and FG repeat domains are the most highly conserved feature between the two systems. Despite the similarities, six of the mammalian nucleoporins had not been described previously.
The greater abundance and relative mass of some nucleoporins, rather than greater diversity, seems to explain much of the size difference between the yeast and mammalian NPCs. The high degree of similarity between these evolutionarily distant NPCs suggests that the basic functions of the NPC are highly conserved, and that the same basic set of building blocks has evolved to handle specialized functions. Some of those adaptations may also pose risks: of the six previously undescribed nucleoporins the authors identified, one is linked to a human genetic disease known as triple-A syndrome.
On page 855, Wasiak et al. describe another project in the burgeoning field of subcellular proteomics, this one focused on clathrin-coated vesicles. The authors uncovered ten novel proteins in vesicle-enriched preparations, and found that one of them interacts with the clathrin adaptors AP1 and GGA2 and may stimulate clathrin assembly. ▪