![]() NPCs serve as a gateway to actively control nucleocytoplasmic exchange of macromolecules such as proteins and RNA ( D'Angelo and Hetzer, 2008). It is perforated with nuclear pore complexes (NPCs), which are composed of proteins known as nucleoporins (Nups). The nuclear envelope consists of two lipid bilayer membranes that compartmentalize the nucleus from the cytosol. These findings offer an opportunity for the development of novel NFAT5 targeting strategies that are potentially useful for the treatment of diseases associated with NFAT5 dysregulation. Our findings have identified an unconventional tonicity-dependent nucleocytoplasmic trafficking pathway for NFAT5 that represents a critical step in orchestrating rapid cellular adaptation to change in extracellular tonicity. Proteomics analysis and siRNA screening further revealed that nuclear export of NFAT5 under hypotonicity is driven by exportin-T (XPOT), where the process requires RuvB-like AAA-type ATPase 2 (RUVBL2) as an indispensable chaperone. siRNA screening revealed that only karyopherin β1 (KPNB1), but not karyopherin α, is responsible for the nuclear import of NFAT5 via direct interaction with the NFAT5-NLS. ![]() We found that NFAT5 utilizes a unique nuclear localization signal (NFAT5-NLS) for nuclear import. Here, we demonstrate that NFAT5 enters the nucleus via the nuclear pore complex. NFAT5 activity is tightly regulated by extracellular tonicity, but the underlying mechanisms remain elusive. It is also implicated in diverse physiological and pathological processes. NFAT5 is the only known mammalian tonicity-responsive transcription factor with an essential role in cellular adaptation to hypertonic stress.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |