Xpo7 is a broad-spectrum exportin and a nuclear import receptor

The Journal of Cell Biology
Metin AksuDirk Görlich

Abstract

Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future.

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Citations

Feb 12, 2019·Cellular and Molecular Life Sciences : CMLS·Paulo A Ferreira
May 8, 2019·Molecular Carcinogenesis·Thomas R HolmesLaura A Hansen
Apr 4, 2019·Annual Review of Biophysics·Bernhard HampoelzMartin Beck
Apr 27, 2019·The Journal of Cell Biology·Arturo Vera RodriguezDirk Görlich
Apr 27, 2019·The Journal of Cell Biology·Metin AksuDirk Görlich
Mar 17, 2020·The EMBO Journal·Bahram KhosraviDieter Edbauer
Mar 8, 2019·Frontiers in Genetics·Anita K Hopper, Regina T Nostramo
Nov 23, 2019·Cancers·Sabrina Ernst, Gerhard Müller-Newen
Nov 25, 2018·Cells·Friederike K Kosyna, Reinhard Depping
Jan 1, 2021·Cellular Signalling·Łukasz MarkiewiczPaweł Niewiadomski
Jan 27, 2021·Journal of Cell Science·Giulia PaciEdward A Lemke
Feb 20, 2021·Genes & Development·Andrew J InnesJesús Gil
Apr 30, 2021·Journal of Cell Science·Joanna KalitaRoderick Y H Lim
Aug 26, 2021·Journal of Cell Science·Giulia PaciEdward A Lemke
May 22, 2021·Brain : a Journal of Neurology·Terouz PashaFrank Hirth

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Methods Mentioned

BETA
RIP
pulldowns
GTPase
transfection
phage display
fluorescence microscopy
pulldown
GTPases
acetylation
gel filtration

Software Mentioned

MaxQuant
Excel
Andromeda
ImageJ
IntAct

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