The carrier Msn5p/Kap142p promotes nuclear export of the hsp70 Ssa4p and relocates in response to stress

Abstract

SummaryCytoplasmic hsp70s like yeast Ssa4p shuttle between nucleus and cytoplasm under normal growth conditions but accumulate in nuclei upon stress. This nuclear accumulation is only transient, and Ssa4p relocates to the cytoplasm when cells recover. We show here that Ssa4p nuclear export is independent of Xpol/Crm1 and identify the importin-b family member Msn5p/Kap142p as the exporter for Ssa4p. In growing cells and in vitro, Msn5p and Ssa4p generate genuine export complexes that require Ran/Gsp1p-GTP. Furthermore, nucleoporin Nup82p, which plays a role in Msn5p-mediated transport, is necessary for efficient export of Ssa4p. In living cells, stress not only regulates Ssa4p localization, but also controls the distribution of Msn5p. Msn5p is concentrated in nuclei of unstressed cells, but appears in the cytoplasm upon exposure to ethanol, heat, starvation or severe oxidative stress. In addition, growth on nonfermentable carbon sources relocates a portion of Msn5p to the cytoplasm and leads to a partial nuclear accumulation of Ssa4p. Taken together, growth and stress conditions that localize the transporter Msn5p to the cytoplasm also induce the nuclear accumulation of its cargo Ssa4p.

Derepression of RNA Polymerase III Transcription by Phosphorylation and Nuclear Export of Its Negative Regulator, Maf1

“…It was shown that whenever Msn5 was detected in the cytoplasm, Saa4 protein, another Msn5 cargo, was concentrated in the nucleus (16). It was suggested that when Msn5 was sequestered in the cytoplasm, it was unable to ferry its cargo from the nucleus.…”

“…It is worth mentioning that the Msn5 carrier, nuclearly localized under standard conditions in glucose, becomes redistributed to the cytoplasm upon transfer to a medium with a nonfermentable carbon source (16). It was shown that whenever Msn5 was detected in the cytoplasm, Saa4 protein, another Msn5 cargo, was concentrated in the nucleus (16).…”

Utp9p Facilitates Msn5p-mediated Nuclear Reexport of Retrograded tRNAs in Saccharomyces cerevisiae

“…Like other ␤-karyopherin export receptors including the nuclear tRNA export receptor Los1p, loading of Msn5p with protein cargo has been shown to be dependent on the Ran GTPase Gsp1p in the GTP bound form (Hellmuth et al, 1998;Quan et al, 2006). Consequently, protein-binding studies were conducted in vitro to ascertain whether the interaction between Msn5p and tRNA is dependent on Gsp1p-GTP ( Figure 14B).…”

Common Genetic Pathways Regulate Organ-Specific Infection-Related Development in the Rice Blast Fungus

“…Msn5p can import or export different proteins and RNAs. Export from the nucleus of the transcription factors Pho4p (Kaffman et al, 1998), Mig1p (DeVit andJohnston, 1999), Msn2p-Msn4p (Gorner et al, 2002), Crz1 (Boustany and Cyert, 2002), Rtg1p-Rtg3p (Komeili et al, 2000), Swi6p (Queralt and Igual, 2003), and other yeast proteins, such as the Cln-Cdc28p inhibitor Far1p (Blondel et al, 1999), the MAPK scaffold protein Ste5 (Mahanty et al, 1999), the chaperone hsp70-Ssa4p (Quan et al, 2006), and the Ho endonuclease (Bakhrat et al, 2008), has been shown to be mediated by Msn5p. In addition, the mammalian Exportin-5 mediates nuclear export of pre-miRNAs (Bohnsack et al, 2004), and Msn5p can also bind short noncoding double-stranded RNAs (Shibata et al, 2006).…”