title: NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes.
abstract: POM121 and gp210 were, until this point, the only known membrane-integral nucleoporins (Nups) of vertebrates and, thus, the only candidate anchors for nuclear pore complexes (NPCs) within the nuclear membrane. In an accompanying study (Stavru et al.), we provided evidence that NPCs can exist independently of POM121 and gp210, and we predicted that vertebrate NPCs contain additional membrane-integral constituents. We identify such an additional membrane protein in the NPCs of mammals, frogs, insects, and nematodes as the orthologue to yeast Ndc1p/Cut11p. Human NDC1 (hNDC1) likely possesses six transmembrane segments, and it is located at the nuclear pore wall. Depletion of hNDC1 from human HeLa cells interferes with the assembly of phenylalanine-glycine repeat Nups into NPCs. The loss of NDC1 function in Caenorhabditis elegans also causes severe NPC defects and very high larval and embryonic mortality. However, it is not ultimately lethal. Instead, homozygous NDC1-deficient worms can be propagated. This indicates that none of the membrane-integral Nups is universally essential for NPC assembly, and suggests that NPC biogenesis is an extremely fault-tolerant process.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Stavru
authors.forename: Bastian B
authors.initials: BB
authors.lastname: Hülsmann
authors.forename: Anne
authors.initials: A
authors.lastname: Spang
authors.forename: Enno
authors.initials: E
authors.lastname: Hartmann
authors.forename: Volker C
authors.initials: VC
authors.lastname: Cordes
authors.forename: Dirk
authors.initials: D
authors.lastname: Görlich
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007814:Larva / Q000235:genetics / Q000254:growth & development; D051379:Mice; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; C510249:NDC1 protein, human; D028861:Nuclear Pore Complex Proteins