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Nucleoporins and Protein Transport in Drosophila
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
2006 (English)Doctoral thesis, monograph (Other academic)
Abstract [en]

Many biological responses rely on the selective translocation of transcriptional regulators in and out of the nucleus through nuclear pore complexes (NPC). More than one million macromolecules per minute pass through the NPC and an important challenge is to understand the coordination of nucleocytoplasmic trafficking. Analysis of nucleoporin function in yeast and higher eukaryotes demonstrated a requirement for many nucleoporins in NPC assembly and RNA or protein transport. However, the mechanistic roles of individual nucleoporins in protein transport are still controversial.

We have identified the Drosophila nucleoporin Nup88 in a screen for mutants disrupting epithelial branch fusion. Nup88 forms a complex with Nup214 and both nucleoporins are interdependent for their localization at the cytoplasmic face of the NPC. Whereas Nup88 is not required for classical protein import, Nup214 is partially required. The major function of the Nup88-Nup214 complex however is to attenuate NES-mediated protein export by anchoring a subfraction of the export receptor CRM1 to the pore. We show that the Rel proteins Dorsal and Dif are substrates of CRM1 and require Nup88 and Nup214 for their nuclear accumulation upon signaling. Our results suggest a new mechanism by which the relative amounts of a nuclear pore subcomplex can regulate the rates of CRM1-mediated protein export.

Biochemical studies have implicated many nucleoporins with the nucleocytoplasmic transport of proteins, but the physiological functions of many NPC components in the process remain unknown. We have inactivated thirty nucleoporins encoded by the Drosophila genome and analyzed the resulting phenotypes on importin β-import and CRM1-export. Depletion of Nup358, Nup54 and Nup153 resulted in defects in the nuclear accumulation of a cNLS-GFP reporter. None of the thirty tested nucleoporins revealed a defect in CRM1-mediated export of GFP-NES. Only the inactivation of RanBP3, a CRM1 co-factor, caused defects in GFP-NES export and localization of CRM1. These phenotypes were restored by simultaneous inactivation of Nup214, implying a new function of RanBP3 in recycling of CRM1 to the nucleus.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2006. , 203 p.
Keyword [en]
NPC, Nucleoporin, Nup88, Nup214, CRM1, Dorsal, Drosophila
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-968ISBN: 91-7155-237-5 (print)OAI: oai:DiVA.org:su-968DiVA: diva2:200746
Public defence
2006-04-28, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Opponent
Supervisors
Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved
List of papers
1. members only encodes a Drosophila nucleoporin required for Rel protein import and immune response activation
Open this publication in new window or tab >>members only encodes a Drosophila nucleoporin required for Rel protein import and immune response activation
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2000 In: Genes and development, ISSN 0890-9369, Vol. 14, no 15, 1945-1957 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25885 (URN)
Note
Part of urn:nbn:se:su:diva-968Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved
2. The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the nuclear envelope and attenuates NES-mediated nuclear export
Open this publication in new window or tab >>The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the nuclear envelope and attenuates NES-mediated nuclear export
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2003 In: Journal of cell biology, ISSN 0021-9525, Vol. 163, no 4, 701-706 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25886 (URN)
Note
Part of urn:nbn:se:su:diva-968Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved
3. Interplay of Nup214 and Nup88 sequesters CRM1 at the nuclear rim and modulates NF-κB activation in Drosophila.
Open this publication in new window or tab >>Interplay of Nup214 and Nup88 sequesters CRM1 at the nuclear rim and modulates NF-κB activation in Drosophila.
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25887 (URN)
Note
Part of urn:nbn:se:su:diva-968Available from: 2006-04-06 Created: 2006-04-06 Last updated: 2010-01-13Bibliographically approved
4. Deciphering nucleoporin functions in nucleocytoplasmic protein transport in Drosophila.
Open this publication in new window or tab >>Deciphering nucleoporin functions in nucleocytoplasmic protein transport in Drosophila.
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25888 (URN)
Note
Part of urn:nbn:se:su:diva-968Available from: 2006-04-06 Created: 2006-04-06 Last updated: 2010-01-13Bibliographically approved

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