Academic Journal
Mechanism of exportin retention in the cell nucleus
| العنوان: | Mechanism of exportin retention in the cell nucleus |
|---|---|
| المؤلفون: | Kapinos, Larisa E., Kalita, Joanna, Kassianidou, Elena, Rencurel, Chantal, Lim, Roderick Y. H. |
| المساهمون: | Biozentrum, Swiss Nanoscience Institute, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Swiss National Science Foundation |
| المصدر: | Journal of Cell Biology ; volume 223, issue 2 ; ISSN 0021-9525 1540-8140 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2024 |
| الوصف: | Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinβ1 (Kapβ1 or importinβ1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapβ1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1083/jcb.202306094 |
| DOI: | 10.1083/jcb.202306094/1923024/jcb_202306094.pdf |
| الاتاحة: | http://dx.doi.org/10.1083/jcb.202306094 https://rupress.org/jcb/article-pdf/doi/10.1083/jcb.202306094/1923024/jcb_202306094.pdf |
| Rights: | http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.FC8F958E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1083/jcb.202306094 |
|---|