bims-nucpor 2022-07-24 papers

Issue of 2022–07–24
four papers selected by
Sara Mingu, Johannes Gutenberg University

Elife. 2022 Jul 19. pii: e75513. [Epub ahead of print]11

Ndc1 drives nuclear pore complex assembly independent of membrane biogenesis to promote nuclear formation and growth.

Michael Sean Mauro, Gunta Celma, Vitaly Zimyanin, Magdalena M Magaj, Kimberley H Gibson, Stefanie Redemann, Shirin Bahmanyar.

The nuclear envelope (NE) assembles and grows from bilayer lipids produced at the endoplasmic reticulum (ER). How ER membrane incorporation coordinates with assembly of nuclear pore complexes (NPCs) to generate a functional NE is not well understood. Here, we use the stereotypical first division of the early C. elegans embryo to test the role of the membrane-associated nucleoporin Ndc1 in coupling NPC assembly to NE formation and growth. 3D-EM tomography of reforming and expanded NEs establishes that Ndc1 determines NPC density. Loss of ndc1 results in faster turnover of the outer scaffold nucleoporin Nup160 at the NE, providing an explanation for how Ndc1 controls NPC number. NE formation fails in the absence of both Ndc1 and the inner ring component Nup53, suggesting partially redundant roles in NPC assembly. Importantly, upregulation of membrane synthesis restored the slow rate of nuclear growth resulting from loss of ndc1 but not from loss of nup53. Thus, membrane biogenesis can be decoupled from Ndc1-mediated NPC assembly to promote nuclear growth. Together, our data suggest that Ndc1 functions in parallel with Nup53 and membrane biogenesis to control NPC density and nuclear size.

Keywords: C. elegans; C. elegans embryos; NDC1; Nup107-160 complex; cell biology; lipid synthesis; nuclear envelope; nuclear pore complex

DOI: https://doi.org/10.7554/eLife.75513

Front Plant Sci. 2022 ;13 903808

MdNup54 Interactions With MdHSP70 Involved in Flowering in Apple.

Chenguang Zhang, XIaoshuang Zhang, Bo Cheng, Junkai Wu, Libin Zhang, Xiao Xiao, Dong Zhang, Caiping Zhao, Na An, Mingyu Han, Libo Xing.

Flowering-related problems in "Fuji" apple have severely restricted the development of China's apple industry. Nuclear pore complexes (NPCs) control nucleoplasmic transport and play an important role in the regulation of plant growth and development. However, the effects of NPCs on apple flowering have not been reported. Here, we analysed the expression and function of MdNup54, a component of apple NPC. MdNup54 expression was the highest in flower buds and maintained during 30-70 days after flowering. MdNup54-overexpressing (OE) Arabidopsis lines displayed significantly earlier flowering than that of the wild type. We further confirmed that MdNup54 interacts with MdHSP70, MdMYB11, and MdKNAT4/6. Consistent with these observations, flowering time of MdHSP70-OE Arabidopsis lines was also significantly earlier. Therefore, our findings suggest a possible interaction of MdNup54 with MdHSP70 to mediate its nuclear and cytoplasmic transport and to regulate apple flowering. The results enhance the understanding of the flowering mechanism in apple and propose a novel strategy to study nucleoporins.

Keywords: MdHSP70; MdNup54; apple; flowering; interaction

DOI: https://doi.org/10.3389/fpls.2022.903808

Cell Rep. 2022 Jul 19. pii: S2211-1247(22)00908-1. [Epub ahead of print]40(3): 111106

Nuclear RNA binding regulates TDP-43 nuclear localization and passive nuclear export.

Lauren Duan, Benjamin L Zaepfel, Vasilisa Aksenova, Mary Dasso, Jeffrey D Rothstein, Petr Kalab, Lindsey R Hayes.

Nuclear clearance of the RNA-binding protein TDP-43 is a hallmark of neurodegeneration and an important therapeutic target. Our current understanding of TDP-43 nucleocytoplasmic transport does not fully explain its predominantly nuclear localization or mislocalization in disease. Here, we show that TDP-43 exits nuclei by passive diffusion, independent of facilitated mRNA export. RNA polymerase II blockade and RNase treatment induce TDP-43 nuclear efflux, suggesting that nuclear RNAs sequester TDP-43 in nuclei and limit its availability for passive export. Induction of TDP-43 nuclear efflux by short, GU-rich oligomers (presumably by outcompeting TDP-43 binding to endogenous nuclear RNAs), and nuclear retention conferred by splicing inhibition, demonstrate that nuclear TDP-43 localization depends on binding to GU-rich nuclear RNAs. Indeed, RNA-binding domain mutations markedly reduce TDP-43 nuclear localization and abolish transcription blockade-induced nuclear efflux. Thus, the nuclear abundance of GU-RNAs, dictated by the balance of transcription, pre-mRNA processing, and RNA export, regulates TDP-43 nuclear localization.

Keywords: CP: Molecular biology; RNA; TDP-43; amyotrophic lateral sclerosis; frontotemporal dementia; neurodegeneration; nuclear transport; splicing; transcription

DOI: https://doi.org/10.1016/j.celrep.2022.111106

Front Neurosci. 2022 ;16 905991

Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice.

Yoshiatsu Aomine, Koki Sakurai, Tom Macpherson, Takaaki Ozawa, Yoichi Miyamoto, Yoshihiro Yoneda, Masahiro Oka, Takatoshi Hikida.

Importin α3 (Gene: Kpna3, the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP) in the KPNA3 gene are associated with the occurrence of several psychiatric disorders accompanied by abnormal reward-related behavior, including schizophrenia, major depression, and substance addiction. However, the precise roles of importin α3 in controlling reward processing and motivation are still unclear. In this study, we evaluated the behavioral effects of Kpna3 knockout (KO) in mice on performance in touchscreen operant chamber-based tasks evaluating simple (fixed-ratio) and effortful (progressive-ratio) reward-seeking behaviors. While Kpna3 KO mice showed no significant differences in operant reward learning on a fixed-ratio schedule, they demonstrated significantly increased motivation (increased break point) to instrumentally respond for sucrose on a progressive-ratio schedule. We additionally measured the number of c-Fos-positive cells, a marker of neural activity, in 20 regions of the brain and identified a network of brain regions based on their interregional correlation coefficients. Network and graph-theoretic analyses suggested that Kpna3 deficiency enhanced overall interregional functional connectivity. These findings suggest the importance of Kpna3 in motivational control and indicate that Kpna3 KO mice may be an attractive line for modeling motivational abnormalities associated with several psychiatric disorders.

Keywords: KPNA; brain network; c-fos; centrality; functional connectivity; importin α; progressive ratio schedule

DOI: https://doi.org/10.3389/fnins.2022.905991