bims-nucpor 2022-01-02 papers

Issue of 2022–01–02
four papers selected by
Sara Mingu, Johannes Gutenberg University

Cell Rep. 2021 Dec 28. pii: S2211-1247(21)01647-8. [Epub ahead of print]37(13): 110151

Association of RanGAP to nuclear pore complex component, RanBP2/Nup358, is required for pupal development in Drosophila.

Shane Chen, Maria Lyanguzova, Ross Kaufhold, Karen M Plevock Haase, Hangnoh Lee, Alexei Arnaoutov, Mary Dasso.

Ran's GTPase-activating protein (RanGAP) is tethered to the nuclear envelope (NE) in multicellular organisms. We investigated the consequences of RanGAP localization in human tissue culture cells and Drosophila. In tissue culture cells, disruption of RanGAP1 NE localization surprisingly has neither obvious impacts on viability nor nucleocytoplasmic transport of a model substrate. In Drosophila, we identified a region within nucleoporin dmRanBP2 required for direct tethering of dmRanGAP to the NE. A dmRanBP2 mutant lacking this region shows no apparent growth defects during larval stages but arrests at the early pupal stage. A direct fusion of dmRanGAP to the dmRanBP2 mutant rescues this arrest, indicating that dmRanGAP recruitment to dmRanBP2 per se is necessary for the pupal ecdysis sequence. Our results indicate that while the NE localization of RanGAP is widely conserved in multicellular organisms, the targeting mechanisms are not. Further, we find a requirement for this localization during pupal development.

Keywords: Drosophila; Nuclear Pore Complex; Ran; RanBP2/Nup358; RanGAP; SUMO1; nuclear transport; pupation

DOI: https://doi.org/10.1016/j.celrep.2021.110151

Viruses. 2021 Dec 15. pii: 2515. [Epub ahead of print]13(12):

Role of HSV-1 Capsid Vertex-Specific Component (CVSC) and Viral Terminal DNA in Capsid Docking at the Nuclear Pore.

José Ramon Villanueva-Valencia, Efthymios Tsimtsirakis, Alex Evilevitch.

Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids forms a structural motif with the portal cap (which retains DNA in the capsid), which mediates capsid-NPC binding. We demonstrate that terminal viral DNA adjacent to the portal proteins does not present a structural element required for capsid-NPC binding. Our data also show that level of CVSC proteins on the HSV-1 capsid affects level of NPC binding. To elucidate the capsid-binding process, we use an isolated, reconstituted cell nucleus system that recapitulates capsid-nucleus binding in vivo without interference from trafficking kinetics of capsids moving toward the nucleus. This allows binding of non-infectious capsid maturation intermediates with varying levels of vertex-specific components. This experimental system provides a platform for investigating virus-host interaction at the nuclear membrane.

Keywords: DNA ejection; HSV-1; UL25; UL36; capsid vertex-specific component (CVSC); nuclear pore complex

DOI: https://doi.org/10.3390/v13122515

Front Oncol. 2021 ;11 784319

In Pursuit of Distinctiveness: Transmembrane Nucleoporins and Their Disease Associations.

Divya Bindra, Ram Kumar Mishra.

The bi-directional nucleocytoplasmic shuttling of macromolecules like molecular signals, transcription factors, regulatory proteins, and RNAs occurs exclusively through Nuclear Pore Complex (NPC) residing in the nuclear membrane. This magnanimous complex is essentially a congregation of ~32 conserved proteins termed Nucleoporins (Nups) present in multiple copies and mostly arranged as subcomplexes to constitute a functional NPC. Nups participate in ancillary functions such as chromatin organization, transcription regulation, DNA damage repair, genome stabilization, and cell cycle control, apart from their central role as nucleocytoplasmic conduits. Thus, Nups exert a role in the maintenance of cellular homeostasis. In mammals, precisely three nucleoporins traverse the nuclear membrane, are called transmembrane Nups (TM-Nups), and are involved in multiple cellular functions. Owing to their vital roles in cellular processes and homeostasis, dysregulation of nucleoporin function is implicated in various diseases. The deregulated functioning of TM-Nups can thus act as an opportune window for the development of diseases. Indeed, mounting evidence exhibits a strong association of TM-Nups in cancer and numerous other physiological disorders. These findings have provided much-needed insights into the novel mechanisms of disease progression. While nucleoporin's functions have often been summarized in the disease context, a focus on TM-Nups has always lacked. This review emphasizes the elucidation of distinct canonical and non-canonical functions of mammalian TM-Nups and the underlying mechanisms of their disease association.

Keywords: NDC1; Nup210; POM121; cancer; nucleoporins

DOI: https://doi.org/10.3389/fonc.2021.784319

Genes Cells. 2021 Dec 25.

Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain.

Kazuya Jibiki, Mo-Yan Liu, Chao-Sen Lei, Takashi S Kodama, Chojiro Kojima, Toshimichi Fujiwara, Noriko Yasuhara.

Importin α has been described as a nuclear protein transport receptor that enables proteins synthesized in the cytoplasm to translocate into the nucleus. Besides its function in nuclear transport, an increasing number of studies have examined its non-nuclear transport functions. In both nuclear transport and non-nuclear transport, a functional domain called the IBB domain (importin β binding domain) plays a key role in regulating importin α behavior, and is a common interacting domain for multiple binding partners. However, it is not yet fully understood how the IBB domain interacts with multiple binding partners, which leads to the switching of importin α function. In this study, we have distinguished the location and propensities of amino acids important for each function of the importin α IBB domain by mapping the biochemical/physicochemical propensities of evolutionarily conserved amino acids of the IBB domain onto the structure associated with each function. We found important residues that are universally conserved for IBB functions across species and family members, in addition to those previously known, as well as residues that are presumed to be responsible for the differences in complex-forming ability among family members and for functional switching.

DOI: https://doi.org/10.1111/gtc.12917