Dissection of the molecular mechanisms that control the nuclear accumulation of transport factors importin-α and CAS in stressed cells

• Published in: Cellular and molecular life sciences : CMLS 2008-06, Vol.65 (11), p.1756-1767
• Main Authors: Kodiha, M., Bański, P., Ho-Wo-Cheong, D., Stochaj, U.
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; alpha Karyopherins - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Nucleus - metabolism; Cellular Apoptosis Susceptibility Protein - metabolism; Cytoplasm - metabolism; Heat-Shock Response; HeLa Cells; Humans; Life Sciences; Nuclear Envelope - metabolism; ran GTP-Binding Protein - metabolism; Research Article
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-008-7588-2

. The physiological state of eukaryotic cells controls nuclear trafficking of numerous cargos. For example, stress results in the inhibition of classical protein import, which is characterized by the redistribution of several transport factors. As such, importin-α and cellular apoptosis susceptibility protein (CAS) accumulate in nuclei of heat-shocked cells; however, the mechanisms underlying this relocation are not fully understood. We now show that heat upregulates the initial docking of importin-α at the nuclear envelope and stimulates the translocation of CAS into the nuclear interior. Moreover, heat exposure compromises the exit of importin-α from nuclei and drastically increases its retention in the nucleoplasm, whereas CAS nuclear exit and retention are less affected. Taken together, our results support the idea that heat shock regulates importin-α and CAS nuclear accumulation at several levels. The combination of different stress-induced changes leads to the nuclear concentration of both transport factors in heat-stressed cells.