Nuclear Pore Complex Remodeling by P75(NTR) Cleavage Controls TGF-β Signaling and Astrocyte Functions

Overview

Journal Nat Neurosci

Date 2015 Jun 30

PMID 26120963

Citations 27

Authors

Christian Schachtrup

Jae Kyu Ryu

Konul Mammadzada

Abdullah S Khan

Peter M Carlton

Alex Perez

Frank Christian

Natacha Le Moan

Eirini Vagena

Bernat Baeza-Raja

Victoria Rafalski

Justin P Chan

Roland Nitschke

Miles D Houslay

Mark H Ellisman

Tony Wyss-Coray

Jorge J Palop

Katerina Akassoglou

Affiliations

Soon will be listed here.

Abstract

Astrocytes modulate neuronal activity and inhibit regeneration. We show that cleaved p75 neurotrophin receptor (p75(NTR)) is a component of the nuclear pore complex (NPC) required for glial scar formation and reduced gamma oscillations in mice via regulation of transforming growth factor (TGF)-β signaling. Cleaved p75(NTR) interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling. Thus, NPC remodeling by regulated intramembrane cleavage of p75(NTR) controls astrocyte-neuronal communication in response to profibrotic factors.

Citing Articles

Non-pharmacological interventions of intermittent fasting and pulsed radiofrequency energy (PRFE) combination therapy promote diabetic wound healing.

Huang Y, Qin P, Zhou P, Long B, Zhang S, Gao R Nutr Diabetes. 2024; 14(1):83.

PMID: 39375333 PMC: 11458794. DOI: 10.1038/s41387-024-00344-9.

Fibrin drives thromboinflammation and neuropathology in COVID-19.

Ryu J, Yan Z, Montano M, Sozmen E, Dixit K, Suryawanshi R Nature. 2024; 633(8031):905-913.

PMID: 39198643 PMC: 11424477. DOI: 10.1038/s41586-024-07873-4.

The p75 neurotrophin receptor attenuates secondary thalamic damage after cortical infarction by promoting angiogenesis.

Peng L, Li K, Li D, Zuo X, Zhan L, Chen M CNS Neurosci Ther. 2024; 30(7):e14875.

PMID: 39072998 PMC: 11284236. DOI: 10.1111/cns.14875.

Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.

Feng D, Zhou J, Liu H, Wu X, Li F, Zhao J Sci Adv. 2022; 8(39):eabq2423.

PMID: 36179025 PMC: 9524825. DOI: 10.1126/sciadv.abq2423.

P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.

Deshpande S, Malik S, Conforti P, Lin J, Chu Y, Nath S Cell Tissue Res. 2021; 387(3):415-431.

PMID: 34698916 PMC: 8975773. DOI: 10.1007/s00441-021-03539-z.

References

Annaert W, Levesque L, Craessaerts K, Dierinck I, Snellings G, Westaway D . Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons. J Cell Biol. 1999; 147(2):277-94. PMC: 2174229. DOI: 10.1083/jcb.147.2.277. View

Parkhurst C, Zampieri N, Chao M . Nuclear localization of the p75 neurotrophin receptor intracellular domain. J Biol Chem. 2009; 285(8):5361-8. PMC: 2820764. DOI: 10.1074/jbc.M109.045054. View

Lawrence A, Bouwer J, Perkins G, Ellisman M . Transform-based backprojection for volume reconstruction of large format electron microscope tilt series. J Struct Biol. 2006; 154(2):144-67. DOI: 10.1016/j.jsb.2005.12.012. View

Verret L, Mann E, Hang G, Barth A, Cobos I, Ho K . Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012; 149(3):708-21. PMC: 3375906. DOI: 10.1016/j.cell.2012.02.046. View

Baeza-Raja B, Li P, Le Moan N, Sachs B, Schachtrup C, Davalos D . p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity. Proc Natl Acad Sci U S A. 2012; 109(15):5838-43. PMC: 3326459. DOI: 10.1073/pnas.1103638109. View

Kreitzer G, Marmorstein A, Okamoto P, Vallee R, Rodriguez-Boulan E . Kinesin and dynamin are required for post-Golgi transport of a plasma-membrane protein. Nat Cell Biol. 2000; 2(2):125-7. DOI: 10.1038/35000081. View

Hanbury R, Charles V, Chen E, Leventhal L, Rosenstein J, Mufson E . Excitotoxic and metabolic damage to the rodent striatum: role of the P75 neurotrophin receptor and glial progenitors. J Comp Neurol. 2002; 444(4):291-305. DOI: 10.1002/cne.10104. View

Sachs B, Baillie G, McCall J, Passino M, Schachtrup C, Wallace D . p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway. J Cell Biol. 2007; 177(6):1119-32. PMC: 2064370. DOI: 10.1083/jcb.200701040. View

Tran E, Wente S . Dynamic nuclear pore complexes: life on the edge. Cell. 2006; 125(6):1041-53. DOI: 10.1016/j.cell.2006.05.027. View

10.

Schmierer B, Hill C . TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007; 8(12):970-82. DOI: 10.1038/nrm2297. View

11.

Schachtrup C, Lu P, Jones L, Lee J, Lu J, Sachs B . Fibrinogen inhibits neurite outgrowth via beta 3 integrin-mediated phosphorylation of the EGF receptor. Proc Natl Acad Sci U S A. 2007; 104(28):11814-9. PMC: 1913857. DOI: 10.1073/pnas.0704045104. View

12.

Le Moan N, Houslay D, Christian F, Houslay M, Akassoglou K . Oxygen-dependent cleavage of the p75 neurotrophin receptor triggers stabilization of HIF-1α. Mol Cell. 2011; 44(3):476-90. PMC: 3212815. DOI: 10.1016/j.molcel.2011.08.033. View

13.

Kim C, Perez A, Perkins G, Ellisman M, Dauer W . A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci U S A. 2010; 107(21):9861-6. PMC: 2906867. DOI: 10.1073/pnas.0912877107. View

14.

Silver J, Miller J . Regeneration beyond the glial scar. Nat Rev Neurosci. 2004; 5(2):146-56. DOI: 10.1038/nrn1326. View

15.

Schachtrup C, Ryu J, Helmrick M, Vagena E, Galanakis D, Degen J . Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage. J Neurosci. 2010; 30(17):5843-54. PMC: 2871011. DOI: 10.1523/JNEUROSCI.0137-10.2010. View

16.

Wyss-Coray T, Feng L, Masliah E, Ruppe M, Lee H, Toggas S . Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta 1. Am J Pathol. 1995; 147(1):53-67. PMC: 1869892. View

17.

Terry L, Wente S . Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot Cell. 2009; 8(12):1814-27. PMC: 2794212. DOI: 10.1128/EC.00225-09. View

18.

Oderfeld-Nowak B, Orzylowska-Sliwinska O, Soltys Z, Zaremba M, Januszewski S, Janeczko K . Concomitant up-regulation of astroglial high and low affinity nerve growth factor receptors in the CA1 hippocampal area following global transient cerebral ischemia in rat. Neuroscience. 2003; 120(1):31-40. DOI: 10.1016/s0306-4522(03)00289-6. View

19.

Sachs B, Akassoglou K . Regulation of cAMP by the p75 neurotrophin receptor: insight into drug design of selective phosphodiesterase inhibitors. Biochem Soc Trans. 2007; 35(Pt 5):1273-7. DOI: 10.1042/BST0351273. View

20.

Frank R . The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports--principles and applications. J Immunol Methods. 2002; 267(1):13-26. DOI: 10.1016/s0022-1759(02)00137-0. View