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

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Exportins mediate the nuclear export of cargo molecules, a process dependent on RanGTP.
• CRM1/Xpo1 is well-characterized due to specific inhibitors like leptomycin B, facilitating cargo validation.
• Limited tools have hindered the in-depth analysis of other exportins, including exportin 7 (Xpo7).

Purpose of the Study:

• To comprehensively investigate the cargo spectrum of exportin 7 (Xpo7).
• To develop novel tools for acute functional inhibition of Xpo7 in cellular systems.
• To validate the identified Xpo7 cargo and elucidate its transport mechanisms.

Main Methods:

• Bioinformatic analysis to predict potential Xpo7 export and import cargoes.
• Development and application of anti-Xpo7 nanobodies for acute functional blockade.
• Cellular transfection assays to assess cargo mislocalization upon Xpo7 inhibition.

Main Results:

• Identification of approximately 200 potential export cargoes and about 30 nuclear import substrates for Xpo7.
• Development of pathway-specific anti-Xpo7 nanobodies that acutely inhibit Xpo7 function in cultured cells.
• Demonstration that Xpo7 inhibition leads to nuclear accumulation of export cargoes and cytoplasmic mislocalization of import substrates.

Conclusions:

• Exportin 7 (Xpo7) functions as a broad-spectrum, bidirectional transporter of nuclear-cytoplasmic cargo.
• The developed anti-Xpo7 nanobodies provide a valuable tool for studying Xpo7 function and validating its cargo.
• This study opens new avenues for detailed investigations into the roles of exportins and importins in nuclear transport.