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Publication

Nucleoporin Seh1 maintains Schwann cell homeostasis by regulating genome stability and necroptosis.

Mei Wu | Man Li | Wei Liu | Minbiao Yan | Li Li | Weichao Ding | Ximing Nian | Wenxiu Dai | Di Sun | Yanqin Zhu | Qiuying Huang | Xiaoyun Lu | Zhiyu Cai | Fan Hong | Xuewen Li | Ling Zhang | Zhixiong Liu | Wei Mo | Xueqin Zhang | Liang Zhang
Cell reports | 2023

Schwann cells play critical roles in peripheral neuropathies; however, the regulatory mechanisms of their homeostasis remain largely unknown. Here, we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis. Expression of Seh1 decreases as mice age. Loss of Seh1 leads to activated immune responses and cell necroptosis. Mice with depletion of Seh1 in Schwann cell lineage develop progressive reduction of Schwann cells in sciatic nerves, predominantly non-myelinating Schwann cells, followed by neural fiber degeneration and malfunction of the sensory and motor system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in Schwann cells. Collectively, our results demonstrate that Seh1 is required for Schwann cell homeostasis by maintaining genome integrity and suggest that decrease of nucleoporins may participate in the pathogenesis of periphery neuropathies.

Pubmed ID: 37453065

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PRDM2 Polyclonal Antibody (antibody)

RRID:AB_2760007

This polyclonal targets PRDM2

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Anti-RIP3 (phospho T231 + S232) antibody [2D7] (antibody)

RRID:AB_2868433

This monoclonal targets phospho-RIP3

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SETDB1 antibody (antibody)

RRID:AB_2186069

This polyclonal targets SETDB1

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Mouse Anti-Ribosomal Protein S6 Monoclonal Antibody, Unconjugated, Clone H-4 (antibody)

RRID:AB_2181030

This monoclonal targets Rps6

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Anti-NEFH/NF200 Antibody (antibody)

RRID:AB_2889947

This monoclonal targets NEFH/NF200

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Anti-NeuN antibody [1B7] - Neuronal Marker (antibody)

RRID:AB_10711040

This monoclonal targets NeuN

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Ki-67 Monoclonal Antibody (SolA15), eBioscience (antibody)

RRID:AB_10854564

This monoclonal targets Ki-67

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NUP107 antibody (antibody)

RRID:AB_10597702

This polyclonal targets NUP107

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Phospho-S6 Ribosomal Protein (Ser235/236) Antibody (antibody)

RRID:AB_331679

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)

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Anti-MLKL (phospho S345) antibody [EPR9515(2)] (antibody)

RRID:AB_2687465

This monoclonal targets MLKL (phospho S345)

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NUP54 antibody (antibody)

RRID:AB_10644484

This polyclonal targets NUP54

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Cleaved Caspase-3 (Asp175) Antibody (antibody)

RRID:AB_2341188

This polyclonal targets Cleaved Caspase-3 (Asp175)

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Anti-MBP Antibody (antibody)

RRID:AB_2665438

This polyclonal targets MBP

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Goat Anti-Mouse IgG Polyclonal antibody, 10nm gold Conjugated (antibody)

RRID:AB_954428

This polyclonal targets Mouse Mouse IgG secondary

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Anti-alpha-Tubulin, clone DM1A (antibody)

RRID:AB_310035

This monoclonal targets alpha-Tubulin clone DM1A

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SETDB1 Monoclonal Antibody (5H6A12) (antibody)

RRID:AB_10988015

This monoclonal targets SETDB1

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Sox-10 (N-20) (antibody)

RRID:AB_2195374

This unknown targets Raised against peptide mapping to N-terminus of sox-10 of human origin

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Oct-6 (C-20) (antibody)

RRID:AB_2268536

This polyclonal targets POU3F1

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Anti-Z-DNA [Z22] (antibody)

RRID:AB_2820286

This monoclonal targets Z-DNA

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Cy3-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)

RRID:AB_2307443

This polyclonal targets IgG (H+L)

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Stat1 p84/p91 (E-23) (antibody)

RRID:AB_632435

This polyclonal targets STAT1

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EHMT1 Polyclonal Antibody (antibody)

RRID:AB_2769285

This polyclonal targets EHMT1

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Phospho-CHEK2-S33/35 pAb (antibody)

RRID:AB_2770997

This polyclonal targets CHEK2

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KAP1 antibody (antibody)

RRID:AB_2732886

This monoclonal targets KAP1

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Nup93 (F-2) (antibody)

RRID:AB_10988261

This monoclonal targets Nup93 (F-2)

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Anti-Histone H3 (tri methyl K9) antibody [EPR16601] - ChIP Grade (antibody)

RRID:AB_2797591

This monoclonal targets Histone H3 (tri methyl K9)

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RIP (D94C12) XP Rabbit mAb (antibody)

RRID:AB_2305314

This monoclonal targets RIP

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Rabbit Anti-Krox-20 Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_291594

This polyclonal targets Krox-20

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SUV39H1 (H-55) (antibody)

RRID:AB_2196717

This polyclonal targets SUV39H1

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RIP3 (B-2) (antibody)

RRID:AB_10992232

This monoclonal targets RIP3 (B-2)

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NUP88 antibody (antibody)

RRID:AB_11183758

This polyclonal targets NUP88

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Oct6-Specific antibody (antibody)

RRID:AB_2167357

This polyclonal targets Oct6-Specific

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Cy5-AffiniPure Donkey Anti-Goat IgG (H+L) (min X Ck,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat Sr Prot) (antibody)

RRID:AB_2340415

This unknown targets Goat IgG (H+L)

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KAP1 antibody (antibody)

RRID:AB_2209890

This polyclonal targets KAP1

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Rabbit Anti-STAT1, CT Polyclonal antibody, Unconjugated (antibody)

RRID:AB_310145

This polyclonal targets STAT1, CT

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TrkA antibody [EP1058Y] (antibody)

RRID:AB_1524514

This monoclonal targets TrkA antibody [EP1058Y]

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Phospho-RIP (Ser166) Antibody (Rodent Specific) (antibody)

RRID:AB_2799000

This unknown targets RIPK1

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Purified anti-Nuclear Pore Complex Proteins (antibody)

RRID:AB_2565026

This monoclonal targets Nuclear Pore Complex Proteins

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Chicken Anti-GFAP Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_304558

This polyclonal targets GFAP - Astrocyte Marker

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gamma H2A.X (phospho S139) antibody [9F3] (antibody)

RRID:AB_470861

This monoclonal targets gamma H2A.X (phospho S139) antibody [9F3]

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Phospho-CHEK1-S317 pAb (antibody)

RRID:AB_2770994

This polyclonal targets CHEK1

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Purified anti-mouse CD68 (antibody)

RRID:AB_2044003

This monoclonal targets CD68

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SEC13 antibody (antibody)

RRID:AB_2186234

This polyclonal targets SEC13

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Cy2-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Rat,Shp Sr Prot) (antibody)

RRID:AB_2340827

This unknown targets Mouse IgG (H+L)

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HA-Tag Antibody (F-7) (antibody)

RRID:AB_627809

This monoclonal targets HA-Tag

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HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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Phospho-S6 Ribosomal Protein (Ser235/236) Antibody (antibody)

RRID:AB_331679

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)

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About

The Stimulating Peripheral Activity to Relieve Conditions (SPARC) effort is the result of National Institutes of Health’s (NIH) drive to map out the neural circuitry responsible for visceral control in higher vertebrates. The SPARC Anatomy Working Group (SAWG) is responsible for the integrity of anatomical knowledge in SPARC

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Maryann Martone, Ph.D.

Department of Neurosciences, School of Medicine

University of California, San Diego

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