bims-nucpor 2022-01-09 papers

Issue of 2022–01–09
three papers selected by
Sara Mingu, Johannes Gutenberg University

Front Cell Dev Biol. 2021 ;9 755847

Arantxa Agote-Arán, Junyan Lin, Izabela Sumara.

Nuclear pore complexes (NPCs) are embedded in the nuclear envelope (NE) where they ensure the transport of macromolecules between the nucleus and the cytoplasm. NPCs are built from nucleoporins (Nups) through a sequential assembly order taking place at two different stages during the cell cycle of mammalian cells: at the end of mitosis and during interphase. In addition, fragile X-related proteins (FXRPs) can interact with several cytoplasmic Nups and facilitate their localization to the NE during interphase likely through a microtubule-dependent mechanism. In the absence of FXRPs or microtubule-based transport, Nups aberrantly localize to the cytoplasm forming the so-called cytoplasmic nucleoporin granules (CNGs), compromising NPCs' function on protein export. However, it remains unknown if Nup synthesis or degradation mechanisms are linked to the FXRP-Nup pathway and if and how the action of FXRPs on Nups is coordinated with the cell cycle progression. Here, we show that Nup localization defects observed in the absence of FXR1 are independent of active protein translation. CNGs are cleared in an autophagy- and proteasome-independent manner, and their presence is restricted to the early G1 phase of the cell cycle. Our results thus suggest that a pool of cytoplasmic Nups exists that contributes to the NPC assembly specifically during early G1 to ensure NPC homeostasis at a short transition from mitosis to the onset of interphase.

Keywords: FXR1; G1 phase; cell cycle; nuclear pore complex; nucleoporins; phase separation

DOI: https://doi.org/10.3389/fcell.2021.755847

Biochim Biophys Acta Mol Cell Res. 2022 Jan 04. pii: S0167-4889(21)00259-7. [Epub ahead of print] 119205

Phase separation of FG-nucleoporins in nuclear pore complexes.

Niharika Nag, Santanu Sasidharan, Vladimir N Uversky, Prakash Saudagar, Timir Tripathi.

A nuclear envelope (NE) is a bilayer membrane that separates and physically isolates the genetic material from the cytoplasm. Nuclear pore complexes (NPCs) are cylindrical structures embedded in the NE and remain the sole channel of communication between the nucleus and the cytoplasm. The interior of NPCs contains densely packed intrinsically disordered FG-nucleoporins (FG-Nups), consequently forming a permeability barrier. This barrier facilitates the selection and specificity of the cargoes that are imported, exported, or shuttled through the NPCs. Recent studies have revealed that FG-Nups undergo the process of liquid-liquid phase separation into liquid droplets. Moreover, these liquid droplets mimic the permeability barrier observed in the interior of NPCs. This review highlights the phase separation of FG-Nups occurring inside the NPCs rooted in the NE. We discuss the phase separation of FG-Nups and compare the different aspects contributing to their phase separation. Furthermore, several diseases caused by the aberrant phase separation of the proteins are examined with respect to NEs. By understanding the fundamental process of phase separation at the nuclear membrane, the review seeks to explore the parameters influencing this phenomenon as well as its importance, ultimately paving the way for better research on the structure-function relationship of biomolecular condensates.

Keywords: Biomolecular condensates; FG-Nups; Intrinsically disordered proteins; Nuclear envelope; Phase separation

DOI: https://doi.org/10.1016/j.bbamcr.2021.119205

Cell. 2021 Dec 29. pii: S0092-8674(21)01453-7. [Epub ahead of print]

Comprehensive structure and functional adaptations of the yeast nuclear pore complex.

Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and transport factors have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We provide evidence for three major NPC variants that may foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies, providing a model of the in situ NPC with a radially expanded inner ring. Our comprehensive model reveals features of the nuclear basket and central transporter, suggests a role for the lumenal Pom152 ring in restricting dilation, and highlights structural plasticity that may be required for transport.

Keywords: NPC evolution; Nuclear pore complex; cryo-electron microscopy; cryo-electron tomography; inner ring dilation; nuclear basket; nucleocytoplasmic transport; nucleoporins; structural isoforms

DOI: https://doi.org/10.1016/j.cell.2021.12.015