RT Journal Article
SR Electronic
T1 The molecular chaperone DNAJB6 provides surveillance of FG-Nups and is required for interphase nuclear pore complex biogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.26.465890
DO 10.1101/2021.10.26.465890
A1 E. F. Elsiena Kuiper
A1 Paola Gallardo
A1 Tessa Bergsma
A1 Muriel Mari
A1 Maiara Kolbe Musskopf
A1 Jeroen Kuipers
A1 Ben N. G. Giepmans
A1 Anton Steen
A1 Liesbeth M. Veenhoff
A1 Harm H. Kampinga
A1 Steven Bergink
YR 2021
UL http://biorxiv.org/content/early/2021/10/27/2021.10.26.465890.abstract
AB Biogenesis of nuclear pore complexes (NPCs) includes the formation of the permeability barrier composed of phenylalanine-glycine-rich nucleoporins (FG-Nups) that regulate the selective passage/crossing of biomolecules. The FG-Nups are intrinsically disordered and prone to liquid-liquid phase separate1,2 and aggregate when isolated3. It has remained largely unclear how FG-Nups are protected from making inappropriate interactions during NPC biogenesis. We found that DNAJB6, a molecular chaperone of the heat shock protein network, formed foci next to NPCs. The number of these foci decreases upon removal of proteins involved in the early steps of interphase NPC biogenesis. Reversely, when this process is stalled in the last steps, the number of DNAJB6-containing foci increases and they could be identified as herniations at the nuclear envelope (NE). Immunoelectron tomography showed that DNAJB6 localizes inside the lumen of the herniations arising at NPC biogenesis intermediates. Interestingly, loss of DNAJB6 results in annulate lamellae, which are structures containing partly assembled NPCs associated with disturbances in NPC biogenesis. We find that DNAJB6 binds to FG-Nups and can prevent the aggregation of the FG-region of several FG-Nups in cells and in vitro. Together, our data show that DNAJB6 provides quality control during NPC biogenesis and is the first molecular chaperone that is involved in the surveillance of native intrinsically disordered proteins, including FG-Nups.Competing Interest StatementThe authors have declared no competing interest.