Nuclear pore complex function is influenced by glycosylation of the transmembrane nucleoporin Pom152p

The regulated transport of proteins across the nuclear envelope occurs through nuclear pore complexes (NPCs), which are comprised of more than 30 different protein subunits termed nucleoporins. While some nucleoporins are glycosylated, little is understood about the role of glycosylation in NPC activity. We have identified loss-of-function alleles of ECM39, encoding a mannosyltransferase, as suppressors of a temperature-sensitive mutation in the gene encoding the FXFG-nucleoporin NUP1. We observe that nup1 cells import nucleophilic proteins more efficiently when ECM39 is absent, suggesting that glycosylation may influence nuclear transport. Conditional nup1 and nup82 mutations are partially suppressed by the glycosylation inhibitor tunicamycin, while nic96 and nup116 alleles are hypersensitive to tunicamycin treatment, further implicating glycosylation in NPC function. Because Pom152p is a glycosylated, transmembrane nucleoporin, we examined genetic interactions between pom152 mutants and nup1. A nup1 deletion is lethal in combination with pom152, as well as with truncations of the N-terminal and transmembrane regions of Pom152p. However, truncations of the N-glycosylated, lumenal domain of Pom152p and pom152 mutants lacking N-linked glycosylation sites are viable in combination with nup1, suppress nup1 temperature sensitivity, and partially suppress the nuclear protein import defects associated with the deletion of NUP1. These data provide compelling evidence for a role for glycosylation in influencing NPC function.

Key Words: glycosylation, mannosyltransferase, nuclear pore complex, nuclear transport, nucleoporin

Online ISSN: 1943-2361  Print ISSN: 0016-6731
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