Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains

Fiserova, J.; Spink, M.; Richards, S.A.; Saunter, C.; Goldberg, M.W.

doi:10.1242/jcs.133272

Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro (2024)
Journal Article
Young, N., Gui, Z., Mustafa, S., Papa, K., Jessop, E., Ruddell, E., …Karakesisoglou, I. (2024). Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro. Cells, 13(11), Article 906. https://doi.org/10.3390/cells13110906

Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises SUN-domain and KASH-domain proteins that directly associate within the nuclear envelope l... Read More about Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro.

The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone. (2023)
Journal Article
Al-Ansari, M., Fitzsimons, T., Wei, W., Goldberg, M. W., Kunieda, T., & Quinlan, R. A. (2024). The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone. Cell Stress and Chaperones, 29(1), 51-65. https://doi.org/10.1016/j.cstres.2023.12.001

The tardigrade Ramazzottius varieornatus has remarkable resilience to a range of environmental stresses. In this study, we have characterised two members of the small heat shock protein (sHSP) family in R. varieornatus, HSP20-3 and HSP20-6. These are... Read More about The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone..

STING nuclear partners contribute to innate immune signaling responses (2021)
Journal Article
Dixon, C. R., Malik, P., de las Heras, J. I., Saiz-Ros, N., de Lima Alves, F., Tingey, M., …Schirmer, E. C. (2021). STING nuclear partners contribute to innate immune signaling responses. iScience, 24(9), https://doi.org/10.1016/j.isci.2021.103055

STimulator of INterferon Genes (STING) is an adaptor for cytoplasmic DNA sensing by cGAMP/cGAS that helps trigger innate immune responses (IIRs). Although STING is mostly localized in the ER, we find a separate inner nuclear membrane pool of STING th... Read More about STING nuclear partners contribute to innate immune signaling responses.

Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro (2021)
Journal Article
Hunter-Featherstone, E., Young, N., Chamberlain, K., Cubillas, P., Hulette, B., Wei, X., …Karakesisoglou, I. (2021). Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro. Cells, 10(5), https://doi.org/10.3390/cells10051177

Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and... Read More about Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro.

Proteomic mapping by rapamycin-dependent targeting of APEX2 identifies binding partners of VAPB at the inner nuclear membrane (2019)
Journal Article
James, C., Müller, M., Goldberg, M. W., Lenz, C., Urlaub, H., & Kehlenbach, R. H. (2019). Proteomic mapping by rapamycin-dependent targeting of APEX2 identifies binding partners of VAPB at the inner nuclear membrane. Journal of Biological Chemistry, 294(44), 16241-16254. https://doi.org/10.1074/jbc.ra118.007283

Vesicle-associated membrane protein–associated protein B (VAPB) is a tail-anchored protein that is present at several contact sites of the endoplasmic reticulum (ER). We now show by immunoelectron microscopy that VAPB also localizes to the inner nucl... Read More about Proteomic mapping by rapamycin-dependent targeting of APEX2 identifies binding partners of VAPB at the inner nuclear membrane.

BFSP1 C-terminal domains released by post-translational processing events can alter significantly the calcium regulation of AQP0 water permeability (2019)
Journal Article
Tapodi, A., Clemens, D., Uwineza, A., Goldberg, M., Thinon, E., Heal, W., …Quinlan, R. (2019). BFSP1 C-terminal domains released by post-translational processing events can alter significantly the calcium regulation of AQP0 water permeability. Experimental Eye Research, 185, Article 107585. https://doi.org/10.1016/j.exer.2019.02.001

BFSP1 (beaded filament structural protein 1, filensin) is a cytoskeletal protein expressed in the eye lens. It binds AQP0 in vitro and its C-terminal sequences have been suggested to regulate the water channel activity of AQP0. A myristoylated fragme... Read More about BFSP1 C-terminal domains released by post-translational processing events can alter significantly the calcium regulation of AQP0 water permeability.

Supramolecular Structures of the Dictyostelium Lamin NE81 (2019)
Journal Article
Grafe, M., Batsios, P., Meyer, I., Lisin, D., Baumann, O., Goldberg, M., & Gräf, R. (2019). Supramolecular Structures of the Dictyostelium Lamin NE81. Cells, 8(2), Article 162. https://doi.org/10.3390/cells8020162

Nuclear lamins are nucleus-specific intermediate filaments (IF) found at the inner nuclear membrane (INM) of the nuclear envelope (NE). Together with nuclear envelope transmembrane proteins, they form the nuclear lamina and are crucial for gene regul... Read More about Supramolecular Structures of the Dictyostelium Lamin NE81.

Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication (2019)
Journal Article
Saiz-Ros, N., Czapiewski, R., Epifano, I., Stevenson, A., Swanson, S., Dixon, C., …Schirmer, E. (2019). Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication. Cells, 8(2), Article 120. https://doi.org/10.3390/cells8020120

The primary envelopment/de-envelopment of Herpes viruses during nuclear exit is poorly understood. In Herpes simplex virus type-1 (HSV-1), proteins pUL31 and pUL34 are critical, while pUS3 and some others contribute; however, efficient membrane fusio... Read More about Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication.

The intestinal intermediate filament network responds to and protects against microbial insults and toxins (2019)
Journal Article
Geisler, F., Coch, R. A., Richardson, C., Goldberg, M., Denecke, B., Bossinger, O., & Leube, R. E. (2019). The intestinal intermediate filament network responds to and protects against microbial insults and toxins. Development, 146(2), Article dev.169482. https://doi.org/10.1242/dev.169482

The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionary conserved forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border suggestive of a protective intracel... Read More about The intestinal intermediate filament network responds to and protects against microbial insults and toxins.

Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution (2018)
Journal Article
Reipert, S., Goldammer, H., Richardson, C., Goldberg, M. W., Hawkins, T. J., Hollergschwandtner, E., …Stierhof, Y. (2018). Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution. Journal of Histochemistry & Cytochemistry, 66(12), 903-921. https://doi.org/10.1369/0022155418786698

For ultrafast fixation of biological samples to avoid artifacts, high-pressure freezing (HPF) followed by freeze substitution (FS) is preferred over chemical fixation at room temperature. After HPF, samples are maintained at low temperature during de... Read More about Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution.

Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson–Gilford progeria syndrome fibroblasts (2018)
Journal Article
Bikkul, M. U., Clements, C. S., Godwin, L. S., Goldberg, M. W., Kill, I. R., & Bridger, J. M. (2018). Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson–Gilford progeria syndrome fibroblasts. Biogerontology, 19(6), 579-602. https://doi.org/10.1007/s10522-018-9758-4

Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal premature ageing disease in children. HGPS is one of several progeroid syndromes caused by mutations in the LMNA gene encoding the nuclear structural proteins lamins A and C. In classic... Read More about Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson–Gilford progeria syndrome fibroblasts.

Nuclear pore complex tethers to the cytoskeleton (2017)
Journal Article
Goldberg, M. W. (2017). Nuclear pore complex tethers to the cytoskeleton. Seminars in Cell and Developmental Biology, 68, 52-58. https://doi.org/10.1016/j.semcdb.2017.06.017

The nuclear envelope is tethered to the cytoskeleton. The best known attachments of all elements of the cytoskeleton are via the so-called LINC complex. However, the nuclear pore complexes, which mediate the transport of soluble and membrane bound mo... Read More about Nuclear pore complex tethers to the cytoskeleton.

Repo-Man/PP1 regulates heterochromatin formation in interphase (2017)
Journal Article
Castro, I., Budzak, J., Di Giacinto, M. L., Ligammari, L., Gokhan, E., Spanos, C., …Vagnarelli, P. (2017). Repo-Man/PP1 regulates heterochromatin formation in interphase. Nature Communications, 8, Article 14048. https://doi.org/10.1038/ncomms14048

Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Rep... Read More about Repo-Man/PP1 regulates heterochromatin formation in interphase.

Phosphorylation Regulates the Endocytic Function of the Yeast Dynamin-Related Protein Vps1 (2015)
Journal Article
Smaczynska-de Rooij, I. I., Marklew, C. J., Allwood, E. G., Palmer, S. E., Booth, W. I., Mishra, R., …Ayscough, K. R. (2016). Phosphorylation Regulates the Endocytic Function of the Yeast Dynamin-Related Protein Vps1. Molecular and Cellular Biology, 36(5), 742-755. https://doi.org/10.1128/mcb.00833-15

The family of dynamin proteins is known to function in many eukaryotic membrane fusion and fission events. The yeast dynamin-related protein Vps1 functions at several stages of membrane trafficking, including Golgi apparatus to endosome and vacuole,... Read More about Phosphorylation Regulates the Endocytic Function of the Yeast Dynamin-Related Protein Vps1.

The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells (2015)
Journal Article
Liu, H., Schneider, H., Recino, A., Richardson, C., Goldberg, M. W., & Rudd, C. E. (2015). The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells. Molecular Cell, 59(5), 840-849. https://doi.org/10.1016/j.molcel.2015.07.015

While immune cell adaptors regulate proximal T cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic med... Read More about The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells.

Xenopus LAP2β protein knockdown affects location of lamin B and nucleoporins and has effect on assembly of cell nucleus and cell viability (2015)
Journal Article
Dubińska-Magiera, M., Chmielewska, M., Kozioł, K., Machowska, M., Hutchison, C. J., Goldberg, M. W., & Rzepecki, R. (2015). Xenopus LAP2β protein knockdown affects location of lamin B and nucleoporins and has effect on assembly of cell nucleus and cell viability. Protoplasma, 253(3), 943-956. https://doi.org/10.1007/s00709-015-0861-y

Xenopus LAP2β protein is the single isoform expressed in XTC cells. The protein localizes on heterochromatin clusters both at the nuclear envelope and inside a cell nucleus. The majority of XLAP2β fraction neither colocalizes with TPX2 protein during... Read More about Xenopus LAP2β protein knockdown affects location of lamin B and nucleoporins and has effect on assembly of cell nucleus and cell viability.

A Charge Swap mutation E461K in the yeast dynamin Vps1 reduces endocytic invagination (2015)
Journal Article
Palmer, S., Smaczynska-de Rooij, I., Marklew, C., Allwood, E., Mishra, R., Goldberg, M., & Ayscough, K. (2015). A Charge Swap mutation E461K in the yeast dynamin Vps1 reduces endocytic invagination. Communicative and Integrative Biology, 8(4), https://doi.org/10.1080/19420889.2015.1051274

Vps1 is the yeast dynamin-like protein that functions during several membrane trafficking events including traffic from Golgi to vacuole, endosomal recycling and endocytosis. Vps1 can also function in peroxisomal fission indicating that its ability t... Read More about A Charge Swap mutation E461K in the yeast dynamin Vps1 reduces endocytic invagination.

A dynamin-actin interaction is required for vesicle scission during endocytosis in yeast (2015)
Journal Article
Palmer, S., Smaczynska-de Rooij, I., Marklew, C., Allwood, E., Mishra, R., Johnson, S., …Ayscough, K. (2015). A dynamin-actin interaction is required for vesicle scission during endocytosis in yeast. Current Biology, 25(7), 868-878. https://doi.org/10.1016/j.cub.2015.01.061

Actin is critical for endocytosis in yeast cells, and also in mammalian cells under tension. However, questions remain as to how force generated through actin polymerization is transmitted to the plasma membrane to drive invagination and scission. He... Read More about A dynamin-actin interaction is required for vesicle scission during endocytosis in yeast.

A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells (2014)
Journal Article
Wu, W., Tholozan, F., Goldberg, M., Bowen, L., Wu, J., & Quinlan, R. (2014). A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells. Experimental Eye Research, 120, 10-14. https://doi.org/10.1016/j.exer.2013.12.004

Fibroblast growth factors play a key role in regulating lens epithelial cell proliferation and differentiation via an anteroposterior gradient that exists between the aqueous and vitreous humours. FGF-2 is the most important for lens epithelial cell... Read More about A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells.

Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains (2014)
Journal Article
Fiserova, J., Spink, M., Richards, S., Saunter, C., & Goldberg, M. (2014). Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains. Journal of Cell Science, 127, 124-136. https://doi.org/10.1242/jcs.133272

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic movement. The central channel contains proteins with phenylalanine-glycine (FG) repeats, or variations (GLFG, glycine-leucine-phenylalanine-glycine). These are ‘intrinsically disordered’ and oft... Read More about Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains.

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