bims-nucpor 2022-01-23 papers

bims-nucpor

Biomed News

on Nuclear pore complex and nucleoporins in stress, aging and disease

Issue of 2022–01–23
six papers selected by
Sara Mingu, Johannes Gutenberg University

Karyopherin-mediated nucleocytoplasmic transport.
One ring doesn't rule them all: Distinct nuclear pore complexes in a single cell.
Nuclear Exportin 1 (XPO1) Binds to the Nuclear Localization/Export Signal of the Turnip Mosaic Virus NIb to Promote Viral Infection.
Autophagy of the Nucleus in Health and Disease.
Location, location, location: subcellular protein partitioning in proteostasis and aging.
Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury.

Nat Rev Mol Cell Biol. 2022 Jan 20.

Karyopherin-mediated nucleocytoplasmic transport.

Casey E Wing, Ho Yee Joyce Fung, Yuh Min Chook.

Efficient and regulated nucleocytoplasmic trafficking of macromolecules to the correct subcellular compartment is critical for proper functions of the eukaryotic cell. The majority of the macromolecular traffic across the nuclear pores is mediated by the Karyopherin-β (or Kap) family of nuclear transport receptors. Work over more than two decades has shed considerable light on how the different Kap family members bring their respective cargoes into the nucleus or the cytoplasm in efficient and highly regulated manners. In this Review, we overview the main features and established functions of Kap family members, describe how Kaps recognize their cargoes and discuss the different ways in which these Kap-cargo interactions can be regulated, highlighting new findings and open questions. We also describe current knowledge of the import and export of the components of three large gene expression machines - the core replisome, RNA polymerase II and the ribosome - pointing out the questions that persist about how such large macromolecular complexes are trafficked to serve their function in a designated subcellular location.

DOI: https://doi.org/10.1038/s41580-021-00446-7
Cell. 2022 Jan 20. pii: S0092-8674(21)01564-6. [Epub ahead of print]185(2): 230-231

One ring doesn't rule them all: Distinct nuclear pore complexes in a single cell.

Megan R McCarthy, C Patrick Lusk.

Determining the structural plasticity and dynamics of nuclear pore complexes (NPCs) are major challenges. In this issue of Cell, Akey et al. present comprehensive NPC structures from in vitro and in vivo preparations, demonstrating multiple NPC forms in single cells while providing insight into the evolutionary origin of NPC architecture.

DOI: https://doi.org/10.1016/j.cell.2021.12.042
Front Microbiol. 2021 ;12 780724

Nuclear Exportin 1 (XPO1) Binds to the Nuclear Localization/Export Signal of the Turnip Mosaic Virus NIb to Promote Viral Infection.

Mingzhen Zhang, Pan Gong, Linhao Ge, Yinzi Li, Zhaoyang Chang, Rui Qiao, Xueping Zhou, Aiming Wang, Fangfang Li.

  The nuclear localization signal (NLS) and nuclear export signal (NES) are key signatures of proteins for controlling nuclear import and export. The NIb protein of turnip mosaic virus (TuMV) is an RNA-dependent RNA polymerase (RdRP) that is absolutely required for viral genome replication. Previous studies have shown that NIb is a nucleocytoplasmic shuttling protein and contains four putative NES and four putative NLS motifs. Here, we analyzed the function of these NESs and NLSs, and identified two functional NESs and one functional NLS. Mutation of the identified functional NESs or NLS inhibited viral RNA accumulation and systemic infection. Exportin 1 (XPO1) is a nuclear export receptor that binds directly to cargo proteins harboring a leucine-rich NES and translocates them to the cytoplasm. We found that XPO1 contains two NIb-binding domains, which recognize the NLS and NES of NIb, respectively, to mediate the nucleocytoplasmic transport of NIb and promote viral infection. Taken together, these data suggest that the nucleocytoplasmic transport of NIb is modulated by XPO1 through its interactions with the functional NLS and NES of NIb to promote viral infection.

Keywords:  NIb; exportin 1 (XPO1); nuclear export signal (NES); nuclear localization signal (NLS); turnip mosaic virus (TuMV)

DOI:  https://doi.org/10.3389/fmicb.2021.780724
Front Cell Dev Biol. 2021 ;9 814955

Autophagy of the Nucleus in Health and Disease.

Georgios Konstantinidis, Nektarios Tavernarakis.

  Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typically excluded during conventional macronucleophagy and micronucleophagy, indicating that degradation of nuclear cargo is tightly regulated. In mammals, similarly to other autophagy subtypes, nucleophagy is crucial for cellular differentiation and development, in addition to enabling cells to respond to various nuclear insults and cell cycle perturbations. A common denominator of all nucleophagic processes characterized in diverse organisms is the dependence on the core autophagic machinery. Here, we survey recent studies investigating the autophagic processing of nuclear components. We discuss nucleophagic events in the context of pathology, such as neurodegeneration, cancer, DNA damage, and ageing.

Keywords:  ageing; autophagy; cancer; neurodegeneration; nucleophagy

DOI:  https://doi.org/10.3389/fcell.2021.814955
Biophys Rev. 2021 Dec;13(6): 931-941

Location, location, location: subcellular protein partitioning in proteostasis and aging.

Anita V Kumar, Louis R Lapierre.

  Somatic maintenance and cell survival rely on proper protein homeostasis to ensure reliable functions across the cell and to prevent proteome collapse. Maintaining protein folding and solubility is central to proteostasis and is coordinated by protein synthesis, chaperoning, and degradation capacities. An emerging aspect that influences proteostasis is the dynamic protein partitioning across different subcellular structures and compartments. Here, we review recent literature related to nucleocytoplasmic partitioning of proteins, nuclear and cytoplasmic quality control mechanisms, and their impact on the development of age-related diseases. We also highlight new points of entry to modulate spatially-regulated proteostatic mechanisms to delay aging.

Keywords:  C. elegans; Nucleocytoplasmic partitioning; Proteostasis

DOI:  https://doi.org/10.1007/s12551-021-00890-x
Front Neurol. 2021 ;12 628811

Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury.

Priya Shukla, Abby Mandalla, Matthew J Elrick, Arun Venkatesan.

  Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage. The clinical and radiologic picture must be distinguished from direct infection of the central nervous system by some viruses, and from metabolic and mitochondrial disorders. Outcomes following ANE are poor overall and worse in those with brainstem involvement. Specific management is often directed toward modulating immune responses given the potential role of systemic inflammation and cytokine storm in potentiating neurologic injury in ANE, though benefits of such approaches remain unclear. The finding that many patients have mutations in the nucleoporin gene RANBP2, which encodes a multifunctional protein that plays a key role in nucleocytoplasmic transport, may allow for the development of disease models that provide insights into pathogenic mechanisms and novel therapeutic approaches.

Keywords:  ANE; COVID-19; RanBP2; encephalitis; influenza; nucleocytoplasmic transport

DOI:  https://doi.org/10.3389/fneur.2021.628811