Molecular determinants of FKBP39 subcellular distribution.

What is it about?

FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins using their peptidyl-prolyl isomerase (PPIase) activity to catalyse the cis-trans conversion of prolyl bonds in proteins during protein-folding events. FKBPs also act as a unique group of histone chaperones. The Drosophila melanogaster peptidyl-prolyl cis-trans isomerase FK506-binding protein of 39 kDa (FKBP39) is thought to act as a transcriptional modulator of gene expression in 20-hydroxyecdysone and juvenile hormone signal transduction. Here, we have shown that the basic domain of FKBP39 possesses a specific nuclear localization signal (NLS) anchored in a putative helix-turn-helix segment. FKBP39 is predominantly a nucleolar protein. We observed that its localization in the nuclear area is highly dynamic. In particular, FKBP39 tagged with a yellow fluorescent protein (YFP) at its N-terminus, in a small population of cells the protein was localized in the nuclear area and appeared as small clusters of visible dots. This pattern, which was observed in all cells analyzed, remained stable during confocal analysis and was reproducible in the performed experiments. The nucleolus often senses cellular stress and is a central hub that coordinates the stress response, which may manifest as nucleolar fragmentation and the subnucleolar structure reorganization. FKBP39 may participate in a nucleolar response that results in such a specific and clearly visible localization pattern associated with a liquid-liquid phase separation (LLPS).

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Why is it important?

The basic domain of FKBP39 possesses a specific nuclear localization signal anchored in a putative helix-turn-helix segment. The nucleoplasmin-like (NPL) core domain of FKBP39 possesses the determinants of the nucleolar-specific localization of the protein. FKBP39 may participate in a nucleolar stress response and the protein may undergo a liquid-liquid phase separation (LLPS).