title: The integral membrane protein Pom34p functionally links nucleoporin subcomplexes.
abstract: Here we have examined the function of Pom34p, a novel membrane protein in Saccharomyces cerevisiae, localized to nuclear pore complexes (NPCs). Membrane topology analysis revealed that Pom34p is a double-pass transmembrane protein with both the amino (N) and carboxy (C) termini positioned on the cytosolic/pore face. The network of genetic interactions between POM34 and genes encoding other nucleoporins was established and showed specific links between Pom34p function and Nup170p, Nup188p, Nup59p, Gle2p, Nup159p, and Nup82p. The transmembrane domains of Pom34p in addition to either the N- or C-terminal region were necessary for its function in different double mutants. We further characterized the pom34deltaN nup188delta mutant and found it to be perturbed in both NPC structure and function. Mislocalization of a subset of nucleoporins harboring phenylalanine-glycine repeats was observed, and nuclear import capacity for the Kap104p and Kap121p pathways was inhibited. In contrast, the pom34delta pom152delta double mutant was viable at all temperatures and showed no such defects. Interestingly, POM152 overexpression suppressed the synthetic lethality of pom34delta nup170delta and pom34delta nup59delta mutants. We speculate that multiple integral membrane proteins, either within the nuclear pore domain or in the nuclear envelope, execute coordinated roles in NPC structure and function.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8240, USA.
authors.forename: Mi
authors.initials: M
authors.lastname: Miao
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ryan
authors.forename: Susan R
authors.initials: SR
authors.lastname: Wente
mesh_terms: D003600:Cytosol / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009685:Nuclear Envelope / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D022022:Nuclear Pore / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; C540867:Pom34 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins