Exportin 7 defines a novel general nuclear export pathway.
Most transport pathways between cell nucleus and cytoplasm are mediated by nuclear transport receptors of the importin beta family. These receptors are in continuous circulation between the two compartments and transfer cargo molecules from one side of the nuclear envelope to the other. RanBP16 is a family member from higher eukaryotes of so far unknown function. We now show that it exports p50RhoGAP from the nucleus and thereby confines this activity to the cytoplasm. It also accounts for nuclear exclusion of 14-3-3sigma, which in turn is known to anchor, for example, cyclin-dependent kinases in the cytoplasm. Our data further suggest that RanBP16 exports several additional cargoes. It thus appears to be a nuclear export mediator with broad substrate specificity and we will therefore refer to it as exportin 7 (Exp7). Finally, we demonstrate that Exp7-dependent nuclear export signals differ fundamentally from the leucine-rich, CRM1-dependent ones: First, they are not just short linear sequences, but instead include folded motifs. Second, basic residues are critical for Exp7 recruitment.
ZMBH, INF 282, Heidelberg, Germany.
José-Manuel
JM
Mingot
Markus T
MT
Bohnsack
Ursula
U
Jäkle
Dirk
D
Görlich
D048948:14-3-3 Proteins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics; D000097606:Exportin 1 Protein
D048948:14-3-3 Proteins; D001224:Aspartic Acid; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D028884:Karyopherins; D008239:Lysine; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C085379:rho GTPase-activating protein