bims-nucpor 2022-11-27 papers

Mov Disord. 2022 Nov 24.

Nuclear Pore Complex Dysfunction in Dystonia Pathogenesis: Nucleoporins in the Spotlight.

Keywords: NUP54; dystonia; nucleoporins; pore complex; torsinA

Int J Biol Macromol. 2022 Nov 16. pii: S0141-8130(22)02705-2. [Epub ahead of print]

Identification of nuclear pore complexes (NPCs) and revealed outer-ring component BnHOS1 related to cold tolerance in B. napus.

Min Song, Bin Linghu, Shuhua Huang, Shengwu Hu, Ran An, Shihao Wei, Jianxin Mu, Yanfeng Zhang.

Nuclear pore complexes (NPCs) consist of ~30 different nucleoporins (Nups), are the unique channels that govern development, hormonal response, and roles in both biotic and abiotic responses, as well as the transport and information exchange of biomacromolecules between nucleoplasms. Here, we report the comprehensive identification of 77 BnNups throughout the zhongshuang11 (ZS11) genome, which were classified into 29 distinct categories based on their evolutionary connections. We compared and contrasted different BnNups by analyzing at their gene structures, protein domains, putative three-dimensional (3D) models and expression patterns. Additional examples of genome-wide duplication events and cross-species synteny are provided to demonstrate the proliferation and evolutionary conservation of BnNups. When BnHOS1 was modified using CRISPR/Cas9 technology, the resulting L10 and L28 lines exhibited substantial freezing resistance. This not only demonstrated the negative regulatory impact of BnHOS1 on cold stress, but also offered a promising candidate gene for cold tolerance breeding and augmented the available B. napus material. These findings not only help us learn more about the composition and function of BnNPCs in B. napus, but they also provide light on how NPCs in other eukaryotic organism functions.

Keywords: BnHOS1; Brassica napus L.; CRISPR/Cas9; Cold tolerance; NPCs; Nups

DOI: https://doi.org/10.1016/j.ijbiomac.2022.11.148

Viruses. 2022 Nov 12. pii: 2503. [Epub ahead of print]14(11):

Tough Way In, Tough Way Out: The Complex Interplay of Host and Viral Factors in Nucleocytoplasmic Trafficking during HIV-1 Infection.

Satarupa Sarkar, Kannan Balakrishnan, Kumaraswami Chintala, Krishnaveni Mohareer, Tom Luedde, Ananda Ayyappan Jaguva Vasudevan, Carsten Münk, Sharmistha Banerjee.

Human immunodeficiency virus-1 (HIV-1) is a retrovirus that integrates its reverse-transcribed genome as proviral DNA into the host genome to establish a successful infection. The viral genome integration requires safeguarding the subviral complexes, reverse transcription complex (RTC) and preintegration complex (PIC), in the cytosol from degradation, presumably effectively secured by the capsid surrounding these complexes. An intact capsid, however, is a large structure, which raises concerns about its translocation from cytoplasm to nucleus crossing the nuclear membrane, guarded by complex nuclear pore structures, which do not allow non-specific transport of large molecules. In addition, the generation of new virions requires the export of incompletely processed viral RNA from the nucleus to the cytoplasm, an event conventionally not permitted through mammalian nuclear membranes. HIV-1 has evolved multiple mechanisms involving redundant host pathways by liaison with the cell's nucleocytoplasmic trafficking system, failure of which would lead to the collapse of the infection cycle. This review aims to assemble the current developments in temporal and spatial events governing nucleocytoplasmic transport of HIV-1 factors. Discoveries are anticipated to serve as the foundation for devising host-directed therapies involving selective abolishment of the critical interactomes between viral proteins and their host equivalents.

Keywords: HIV-1; HIV-1 Rev; capsid import; nucleocytoplasmic trafficking; nucleoporins; viral mRNA export

DOI: https://doi.org/10.3390/v14112503

Int J Mol Sci. 2022 Nov 15. pii: 14103. [Epub ahead of print]23(22):

Identification of the Karyopherin Superfamily in Maize and Its Functional Cues in Plant Development.

Lu Jin, Guobin Zhang, Guixiao Yang, Jiaqiang Dong.

Appropriate nucleo-cytoplasmic partitioning of proteins is a vital regulatory mechanism in phytohormone signaling and plant development. However, how this is achieved remains incompletely understood. The Karyopherin (KAP) superfamily is critical for separating the biological processes in the nucleus from those in the cytoplasm. The KAP superfamily is divided into Importin α (IMPα) and Importin β (IMPβ) families and includes the core components in mediating nucleocytoplasmic transport. Recent reports suggest the KAPs play crucial regulatory roles in Arabidopsis development and stress response by regulating the nucleo-cytoplasmic transport of members in hormone signaling. However, the KAP members and their associated molecular mechanisms are still poorly understood in maize. Therefore, we first identified seven IMPα and twenty-seven IMPβ genes in the maize genome and described their evolution traits and the recognition rules for substrates with nuclear localization signals (NLSs) or nuclear export signals (NESs) in plants. Next, we searched for the protein interaction partners of the ZmKAPs and selected the ones with Arabidopsis orthologs functioning in auxin biosynthesis, transport, and signaling to predict their potential function. Finally, we found that several ZmKAPs share similar expression patterns with their interacting proteins, implying their function in root development. Overall, this article focuses on the Karyopherin superfamily in maize and starts with this entry point by systematically comprehending the KAP-mediated nucleo-cytoplasmic transport process in plants, and then predicts the function of the ZmKAPs during maize development, with a perspective on a closely associated regulatory mechanism between the nucleo-cytoplasmic transport and the phytohormone network.

Keywords: Importin α; Importin β; Karyopherin; NES; NLS; auxin; maize; nucleo-cytoplasmic transport; phytohormone signaling; root development

DOI: https://doi.org/10.3390/ijms232214103

Int J Mol Sci. 2022 Nov 11. pii: 13899. [Epub ahead of print]23(22):

Conservation of Importin α Function in Apicomplexans: Ivermectin and GW5074 Target Plasmodium falciparum Importin α and Inhibit Parasite Growth in Culture.

Sujata B Walunj, Chunxiao Wang, Kylie M Wagstaff, Swati Patankar, David A Jans.

Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily of nuclear transporters is critical to the eukaryotic function and a point of therapeutic intervention with the potential to limit disease progression and pathogenic outcomes. Although the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii both retain unique IMPα genes that are essential, a detailed analysis of their properties has not been performed. As a first step to validate apicomplexan IMPα as a target, we set out to compare the properties of P. falciparum and T. gondii IMPα (PfIMPα and TgIMPα, respectively) to those of mammalian IMPα, as exemplified by Mus musculus IMPα (MmIMPα). Close similarities were evident, with all three showing high-affinity binding to modular nuclear localisation signals (NLSs) from apicomplexans as well as Simian virus SV40 large tumour antigen (T-ag). PfIMPα and TgIMPα were also capable of binding to mammalian IMPβ1 (MmIMPβ1) with high affinity; strikingly, NLS binding by PfIMPα and TgIMPα could be inhibited by the mammalian IMPα targeting small molecules ivermectin and GW5074 through direct binding to PfIMPα and TgIMPα to perturb the α-helical structure. Importantly, GW5074 could be shown for the first time to resemble ivermectin in being able to limit growth of P. falciparum. The results confirm apicomplexan IMPα as a viable target for the development of therapeutics, with agents targeting it worthy of further consideration as an antimalarial.

Keywords: importins; malaria; nuclear import; nuclear import inhibitors; toxoplasmosis

DOI: https://doi.org/10.3390/ijms232213899

Sci Rep. 2022 Nov 23. 12(1): 20171

A mass spectrometry-based approach for the identification of Kpnβ1 binding partners in cancer cells.

Michael O Okpara, Clemens Hermann, Pauline J van der Watt, Shaun Garnett, Jonathan M Blackburn, Virna D Leaner.

Karyopherin beta 1 (Kpnβ1) is the principal nuclear importer of cargo proteins and plays a role in many cellular processes. Its expression is upregulated in cancer and essential for cancer cell viability, thus the identification of its binding partners might help in the discovery of anti-cancer therapeutic targets and cancer biomarkers. Herein, we applied immunoprecipitation coupled to mass spectrometry (IP-MS) to identify Kpnβ1 binding partners in normal and cancer cells. IP-MS identified 100 potential Kpnβ1 binding partners in non-cancer hTERT-RPE1, 179 in HeLa cervical cancer, 147 in WHCO5 oesophageal cancer and 176 in KYSE30 oesophageal cancer cells, including expected and novel interaction partners. 38 binding proteins were identified in all cell lines, with the majority involved in RNA metabolism. 18 binding proteins were unique to the cancer cells, with many involved in protein translation. Western blot analysis validated the interaction of known and novel binding partners with Kpnβ1 and revealed enriched interactions between Kpnβ1 and select proteins in cancer cells, including proteins involved in cancer development, such as Kpnα2, Ran, CRM1, CCAR1 and FUBP1. Together, this study shows that Kpnβ1 interacts with numerous proteins, and its enhanced interaction with certain proteins in cancer cells likely contributes to the cancer state.

DOI: https://doi.org/10.1038/s41598-022-24194-6