Distinct functions of the Drosophila Nup153 and Nup214 FG domains in nuclear protein transport.
The phenylanine-glycine (FG)-rich regions of several nucleoporins both bind to nuclear transport receptors and collectively provide a diffusion barrier to the nuclear pores. However, the in vivo roles of FG nucleoporins in transport remain unclear. We have inactivated 30 putative nucleoporins in cultured Drosophila melanogaster S2 cells by RNA interference and analyzed the phenotypes on importin alpha/beta-mediated import and CRM1-dependent protein export. The fly homologues of FG nucleoporins Nup358, Nup153, and Nup54 are selectively required for import. The FG repeats of Nup153 are necessary for its function in transport, whereas the remainder of the protein maintains pore integrity. Inactivation of the CRM1 cofactor RanBP3 decreased the nuclear accumulation of CRM1 and protein export. We report a surprisingly antagonistic relationship between RanBP3 and the Nup214 FG region in determining CRM1 localization and its function in protein export. Our data suggest that peripheral metazoan FG nucleoporins have distinct functions in nuclear protein transport events.
Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
Nafiseh
N
Sabri
Peggy
P
Roth
Nikos
N
Xylourgidis
Fatemeh
F
Sadeghifar
Jeremy
J
Adler
Christos
C
Samakovlis
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference
D029721:Drosophila Proteins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C523209:Nup153 protein, Drosophila; C490094:Nup214 protein, Drosophila; C094493:ran-binding protein 2