bims-nucpor 2021-11-21 papers

Issue of 2021–11–21
five papers selected by
Sara Mingu, Johannes Gutenberg University

Trends Cell Biol. 2021 Nov 12. pii: S0962-8924(21)00202-6. [Epub ahead of print]

Nuclear pore complex maintenance and implications for age-related diseases.

Nuclear pore complexes (NPCs) bridge the nucleus and the cytoplasm and are indispensable for crucial cellular activities, such as bidirectional molecular trafficking and gene transcription regulation. The discovery of long-lived proteins (LLPs) in NPCs from postmitotic cells raises the exciting possibility that the maintenance of NPC integrity might play an inherent role in lifelong cell function. Age-dependent deterioration of NPCs and loss of nuclear integrity have been linked to age-related decline in postmitotic cell function and degenerative diseases. In this review, we discuss our current understanding of NPC maintenance in proliferating and postmitotic cells, and how malfunction of nucleoporins (Nups) might contribute to the pathogenesis of various neurodegenerative and cardiovascular diseases.

Keywords: aging; neurodegenerative diseases; nuclear pore complex; protein turnover

DOI: https://doi.org/10.1016/j.tcb.2021.10.001

Phytopathology. 2021 Nov 16.

The importin FgPse1 is required for vegetative development, virulence and DON production by interacting with the nuclear polyadenylated RNA-binding protein FgNab2 in Fusarium graminearum.

Lixin Zhang, Kewei Sun, Yiqing Li, Tianling Ma, Y U Zhang, Y N Yin, Shuai Zhang, Wenyong Shao.

Karyopherins are involved in transport through nuclear pore complexes. Karyopherins are required for nuclear import and export pathways by binding to their cargos. Polyadenylation of mRNA is required for various biological processes by regulating gene expression in eukaryotes. Until now, the association of karyopherin with mRNA polyadenylation has been less understood in plant pathogenic fungi. In our study, we focused on the biological functions of the karyopherin FgPse1 in Fusarium graminearum. The results showed that FgPse1 is involved in mycelial growth, asexual reproduction, virulence and DON production. Co-IP and BiFC showed that FgPse1 interacts with the nuclear polyadenylated RNA-binding protein FgNab2. Moreover, a fluorescence localization assay indicated that FgPse1 is required for the nuclear import of FgNab2. The nuclear import of FgNab2 regulates the expression of FgTri4, FgTri5 and FgTri6, which are essential for DON production. Thus, ΔFgPse1 and ΔFgNab2 showed consistent defects in DON production. In summary, our data indicated that FgPse1 is required for mycelial growth, virulence and DON production by interacting with FgNab2 in F. graminearum. These results contribute to improving our understanding of the functions of importins in phytopathogenic fungi.

Keywords: Chemical Control; Disease Control and Pest Management; Fungal Pathogens; Genetics

DOI: https://doi.org/10.1094/PHYTO-08-21-0357-R

J Cell Biol. 2021 Dec 06. pii: e202103036. [Epub ahead of print]220(12):

Phosphorylation-dependent mitotic SUMOylation drives nuclear envelope-chromatin interactions.

Christopher Ptak, Natasha O Saik, Ashwini Premashankar, Diego L Lapetina, John D Aitchison, Ben Montpetit, Richard W Wozniak.

In eukaryotes, chromatin binding to the inner nuclear membrane (INM) and nuclear pore complexes (NPCs) contributes to spatial organization of the genome and epigenetic programs important for gene expression. In mitosis, chromatin-nuclear envelope (NE) interactions are lost and then formed again as sister chromosomes segregate to postmitotic nuclei. Investigating these processes in S. cerevisiae, we identified temporally and spatially controlled phosphorylation-dependent SUMOylation events that positively regulate postmetaphase chromatin association with the NE. Our work establishes a phosphorylation-mediated targeting mechanism of the SUMO ligase Siz2 to the INM during mitosis, where Siz2 binds to and SUMOylates the VAP protein Scs2. The recruitment of Siz2 through Scs2 is further responsible for a wave of SUMOylation along the INM that supports the assembly and anchorage of subtelomeric chromatin at the INM and localization of an active gene (INO1) to NPCs during the later stages of mitosis and into G1-phase.

DOI: https://doi.org/10.1083/jcb.202103036

PLoS Genet. 2021 Nov 18. 17(11): e1009899

Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells.

Miao Chen, Qian Long, Melinda S Borrie, Haohui Sun, Changlin Zhang, Han Yang, Dingbo Shi, Marc R Gartenberg, Wuguo Deng.

The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export. TPR expression is significantly increased in lung cancer tissues and correlated with poor prognosis. Consistently, knockdown of TPR inhibits tRNA nuclear export, protein synthesis and cell growth in lung cancer cell lines. We further show that NXF1, a well-known mRNA nuclear export factor, associates with tRNAs and mediates their transport through nuclear pores. Collectively, our findings uncover a conserved mechanism that regulates nuclear export of tRNAs, which is a limiting step in protein synthesis in eukaryotes.

DOI: https://doi.org/10.1371/journal.pgen.1009899

Mol Med Rep. 2022 Jan;pii: 14. [Epub ahead of print]25(1):

Shuttling of cellular proteins between the plasma membrane and nucleus (Review).

Hua-Chuan Zheng, Hua-Mao Jiang.

Recently accumulated evidence has indicated that the nucleomembrane shuttling of cellular proteins is common, which provides new insight into the subcellular translocation and biological functions of proteins synthesized in the cytoplasm. The present study aimed to clarify the trafficking of proteins between the plasma membrane and nucleus. These proteins primarily consist of transmembrane receptors, membrane adaptor proteins, adhesive proteins, signal proteins and nuclear proteins, which contribute to proliferation, apoptosis, chemoresistance, adhesion, migration and gene expression. The proteins frequently undergo cross‑talk, such as the interaction of transmembrane proteins with signal proteins. The transmembrane proteins undergo endocytosis, infusion into organelles or proteolysis into soluble forms for import into the nucleus, while nuclear proteins interact with membrane proteins or act as receptors. The nucleocytosolic translocation involves export or import through nuclear membrane pores by importin or exportin. Nuclear proteins generally interact with other transcription factors, and then binding to the promoter for gene expression, while membrane proteins are responsible for signal initiation by binding to other membrane and/or adaptor proteins. Protein translocation occurs in a cell‑specific manner and is closely linked to cellular biological events. The present review aimed to improve understanding of cytosolic protein shuttling between the plasma membrane and nucleus and the associated signaling pathways.

Keywords: nucleus; plasma membrane; signal pathway; subcellular shuttling

DOI: https://doi.org/10.3892/mmr.2021.12530