bims-nucpor 2024-03-31 papers

Issue of 2024‒03‒31
three papers selected by
Sara Mingu, Johannes Gutenberg University

Chin J Dent Res. 2024 Mar 28. 27(1): 39-46

Characteristic and Import Mechanism of Protein Nuclear Translocation.

Coordination and information exchange among the various organelles ensure the precise and orderly functioning of eukaryotic cells. Interaction between the cytoplasm and nucleoplasm is crucial for many physiological processes. Macromolecular protein transport into the nucleus requires assistance from the nuclear transport system. These proteins typically contain a nuclear localisation sequence that guides them to enter the nucleus. Understanding the mechanism of nuclear import of macromolecular proteins is important for comprehending cellular processes. Investigation of disease-related alterations can facilitate the development of novel therapeutic strategies and provide additional evidence for clinical trials. This review provides an overview of the proteins involved in nuclear transport and the mechanisms underlying macromolecular protein transport.

Keywords: karyopherin; nuclear import; nuclear localisation sequence; nuclear pore complex; nucleocytoplasmic transport

DOI: https://doi.org/10.3290/j.cjdr.b5136729

Nucleus. 2024 Dec;15(1): 2330947

Mechanobiology of the nucleus during the G2-M transition.

Joana T Lima, Jorge G Ferreira.

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

Keywords: Chromosome; G2-M transition; LINC complex; mechanotransduction; nuclear envelope; nuclear pore complex; nucleus

DOI: https://doi.org/10.1080/19491034.2024.2330947

Commun Biol. 2024 Mar 28. 7(1): 376

The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.

M E Cicardi, V Kankate, S Sriramoji, K Krishnamurthy, S S Markandaiah, B M Verdone, A Girdhar, A Nelson, L B Rivas, A Boehringer, A R Haeusler, P Pasinelli, L Guo, D Trotti.

Expanded intronic G4C2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapβ2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapβ2 is detrimental to their survival, whereas increased Kapβ2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapβ2 levels did not restore TDP-43 into the nucleus, nor did alter the dynamic properties of GR aggregates. Overall, our findings support the design of therapeutic strategies aimed at up-regulating Kapβ2 expression levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD.

DOI: https://doi.org/10.1038/s42003-024-06071-2