The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells.
Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in the nuclear envelope (NE), through which exchange of molecules between the nucleus and cytosol occurs. Biogenesis of NPCs is complex and poorly understood. In particular, almost nothing is known about how NPCs are anchored in the NE. Here, we characterize vertebrate NDC1--a transmembrane nucleoporin conserved between yeast and metazoans. We show by RNA interference (RNAi) and biochemical depletion that NDC1 plays an important role in NPC and NE assembly in vivo and in vitro. RNAi experiments suggest a functional link between NDC1 and the soluble nucleoporins Nup93, Nup53, and Nup205. Importantly, NDC1 interacts with Nup53 in vitro. This suggests that NDC1 function involves forming a link between the NE membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane.
Mansfeld
Jörg
J
Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
Güttinger
Stephan
S
Hawryluk-Gara
Lisa A
LA
Panté
Nelly
N
Mall
Moritz
M
Galy
Vincent
V
Haselmann
Uta
U
Mühlhäusser
Petra
P
Wozniak
Richard W
RW
Mattaj
Iain W
IW
Kutay
Ulrike
U
Antonin
Wolfram
W
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D011510:Proteolipids; D034741:RNA, Small Interfering / Q000494:pharmacology; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism
C510250:NDC1 protein, Xenopus; C510249:NDC1 protein, human; D028861:Nuclear Pore Complex Proteins; C109329:Nup93 protein, Xenopus; C508154:Nup93 protein, human; D010446:Peptide Fragments; D011510:Proteolipids; D034741:RNA, Small Interfering; D029867:Xenopus Proteins; C020485:proteoliposomes