bims-nucpor 2022-03-06 papers

Issue of 2022–03–06
three papers selected by
Sara Mingu, Johannes Gutenberg University

J Neurol Sci. 2022 Feb 16. pii: S0022-510X(22)00049-1. [Epub ahead of print]436 120187

Nuclear pore destruction and loss of nuclear TDP-43 in FUS mutation-related amyotrophic lateral sclerosis motor neurons.

Hitoshi Aizawa, Sayaka Teramoto, Takuto Hideyama, Haruhisa Kato, Hiroo Terashi, Yasuhiro Suzuki, Takashi Kimura, Shin Kwak.

Keywords: Amyotrophic lateral sclerosis; Fused in sarcoma; Nuclear pore complex; Nucleoporin; TDP-43

DOI: https://doi.org/10.1016/j.jns.2022.120187

Elife. 2022 Mar 01. pii: e74714. [Epub ahead of print]11

Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment.

James M Gibson, Heying Cui, M Yusuf Ali, Xioaxin Zhao, Erik W Debler, Jing Zhao, Kathleen M Trybus, Sozanne R Solmaz, Chunyu Wang.

Nup358, a protein of the nuclear pore complex, facilitates a nuclear positioning pathway that is essential for many biological processes, including neuromuscular and brain development. Nup358 interacts with the dynein adaptor Bicaudal D2 (BicD2), which in turn recruits the dynein machinery to position the nucleus. However, the molecular mechanisms of the Nup358/BicD2 interaction and the activation of transport remain poorly understood. Here for the first time, we show that a minimal Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance (NMR) titration and chemical exchange saturation transfer (CEST), mutagenesis and circular dichroism spectroscopy (CD), a Nup358 a-helix encompassing residues 2162-2184 was identified, which transitioned from a random coil to an a-helical conformation upon BicD2-binding and formed the core of the Nup358-BicD2 interface. Mutations in this region of Nup358 decreased the Nup358/BicD2 interaction, resulting in decreased dynein recruitment and impaired motility. BicD2 thus recognizes Nup358 though a 'cargo recognition a-helix', a structural feature that may stabilize BicD2 in its activated state and promote processive dynein motility.

Keywords: molecular biophysics; none; structural biology

DOI: https://doi.org/10.7554/eLife.74714

Nat Commun. 2022 Mar 04. 13(1): 1174

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP.

María García-García, Sara Sánchez-Perales, Patricia Jarabo, Enrique Calvo, Trevor Huyton, Liran Fu, Sheung Chun Ng, Laura Sotodosos-Alonso, Jesús Vázquez, Sergio Casas-Tintó, Dirk Görlich, Asier Echarri, Miguel A Del Pozo.

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.

DOI: https://doi.org/10.1038/s41467-022-28693-y