Tonic ATP-mediated growth suppression in peripheral nerve glia requires arrestin-PP2 and is evaded in NF1

被引：8

作者：

Coover, Robert A. ^{[1
]}

Healy, Tabitha E. ^{[1
]}

Guo, Li ^{[1
]}

Chaney, Katherine E. ^{[1
]}

Hennigan, Robert F. ^{[1
]}

Thomson, Craig S. ^{[1
]}

Aschbacher-Smith, Lindsey E. ^{[1
]}

Jankowski, Michael P. ^{[2
,3
]}

Ratner, Nancy ^{[1
]}

机构：

[1] Cincinnati Childrens Hosp, Div Expt Hematol & Canc Biol, 3333 Burnet Ave,ML 7017, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Hosp, Div Pain Management, Dept Anesthesia, Cincinnati, OH 45229 USA

[3] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45229 USA

来源：

ACTA NEUROPATHOLOGICA COMMUNICATIONS | 2018年 / 6卷

关键词：

Glia; Schwann; PP2A; AKT; Purinergic; Neurofibromatosis; P2Y2; Arrestin; ATP; SCHWANN-CELL PROLIFERATION; WALLERIAN DEGENERATION; BETA-ARRESTINS; NEURAL CREST; RECEPTOR; ACTIVATION; NEUROFIBROMATOSIS; ADENOSINE; PLEXIFORM; PATHWAY;

D O I：

10.1186/s40478-018-0635-9

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Normal Schwann cells (SCs) are quiescent in adult nerves, when ATP is released from the nerve in an activity dependent manner. We find that suppressing nerve activity in adult nerves causes SC to enter the cell cycle. In vitro, ATP activates the SC G-protein coupled receptor (GPCR) P2Y2. Downstream of P2Y2, -arrestin-mediated signaling results in PP2-mediated de-phosphorylation of AKT, and PP2 activity is required for SC growth suppression. NF1 deficient SC show reduced growth suppression by ATP, and are resistant to the effects of -arrestin-mediated signaling, including PP2-mediated de-phosphorylation of AKT. In patients with the disorder Neurofibromatosis type 1, NF1 mutant SCs proliferate and form SC tumors called neurofibromas. Elevating ATP levels in vivo reduced neurofibroma cell proliferation. Thus, the low proliferation characteristic of differentiated adult peripheral nerve may require ongoing, nerve activity-dependent, ATP. Additionally, we identify a mechanism through which NF1 SCs may evade growth suppression in nerve tumors.

引用

页数：15

共 94 条

[51] Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion [J].

Madry, Christian ;

Arancibia-Carcamo, I. Lorena ;

Kyrargyri, Vasiliki ;

Chan, Victor T. T. ;

Hamilton, Nicola B. ;

Attwell, David .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (07) :E1608-E1617

[52] Caveolin-1 Regulates the P2Y2 Receptor Signaling in Human 1321N1 Astrocytoma Cells [J].

Martinez, Namyr A. ;

Ayala, Alondra M. ;

Martinez, Magdiel ;

Martinez-Rivera, Freddyson J. ;

Miranda, Jorge D. ;

Silva, Walter I. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (23) :12208-12222

[53] A microcapsule technique for long-term conduction block of the sciatic nerve by tetrodotoxin [J].

Martinov, VN ;

Nja, A .

JOURNAL OF NEUROSCIENCE METHODS, 2005, 141 (02) :199-205

[54] Absence of Neurofibromin Induces an Oncogenic Metabolic Switch via Mitochondrial ERK-Mediated Phosphorylation of the Chaperone TRAP1 [J].

Masgras, Ionica ;

Ciscato, Francesco ;

Brunati, Anna Maria ;

Tibaldi, Elena ;

Indraccolo, Stefano ;

Curtarello, Matteo ;

Chiara, Federica ;

Cannino, Giuseppe ;

Papaleo, Elena ;

Lambrughi, Matteo ;

Guzzo, Giulia ;

Gambalunga, Alberto ;

Pizzi, Marco ;

Guzzardo, Vincenza ;

Rugge, Massimo ;

Vuljan, Stefania Edith ;

Calabrese, Fiorella ;

Bernardi, Paolo ;

Rasola, Andrea .

CELL REPORTS, 2017, 18 (03) :659-672

[55] Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1 [J].

Mautner, Victor-F. ;

Asuagbor, Florence A. ;

Dombi, Eva ;

Fuensterer, Carsten ;

Kluwe, Lan ;

Wenzel, Ralf ;

Widemann, Brigitte C. ;

Friedman, Jan M. .

NEURO-ONCOLOGY, 2008, 10 (04) :593-598

[56] Protein Kinase A-mediated Gating of Neuregulin-dependent ErbB2-ErbB3 Activation Underlies the Synergistic Action of cAMP on Schwann Cell Proliferation [J].

Monje, Paula V. ;

Athauda, Gagani ;

Wood, Patrick M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (49) :34087-34100

[57]

Morris GE, 2012, AM J PHYSIOL-CELL PH, V302, pC723, DOI [10.1152/ajpcell.00202.2011, 10.1152/ajpcell.00202.2011.]

[58] Physical interaction between neurofibromin and serotonin 5-HT6 receptor promotes receptor constitutive activity [J].

Nadim, Wissem Deraredj ;

Chaumont-Dubel, Severine ;

Madouri, Fahima ;

Cobret, Laetitia ;

De Tauzia, Marie-Ludivine ;

Zajdel, Pawel ;

Benedetti, Helene ;

Marin, Philippe ;

Morisset-Lopez, Severine .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (43) :12310-12315

[59] PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells [J].

Neviani, Paolo ;

Harb, Jason G. ;

Oaks, Joshua J. ;

Santhanam, Ramasamy ;

Walker, Christopher J. ;

Ellis, Justin J. ;

Ferenchak, Gregory ;

Dorrance, Adrienne M. ;

Paisie, Carolyn A. ;

Eiring, Anna M. ;

Ma, Yihui ;

Mao, Hsiaoyin C. ;

Zhang, Bin ;

Wunderlich, Mark ;

May, Philippa C. ;

Sun, Chaode ;

Saddoughi, Sahar A. ;

Bielawski, Jacek ;

Blum, William ;

Klisovic, Rebecca B. ;

Solt, Janelle A. ;

Byrd, John C. ;

Volinia, Stefano ;

Cortes, Jorge ;

Huettner, Claudia S. ;

Koschmieder, Steffen ;

Holyoake, Tessa L. ;

Devine, Steven ;

Caligiuri, Michael A. ;

Croce, Carlo M. ;

Garzon, Ramiro ;

Ogretmen, Besim ;

Arlinghaus, Ralph B. ;

Chen, Ching-Shih ;

Bittman, Robert ;

Hokland, Peter ;

Roy, Denis-Claude ;

Milojkovic, Dragana ;

Apperley, Jane ;

Goldman, John M. ;

Reid, Alistair ;

Mulloy, James C. ;

Bhatia, Ravi ;

Marcucci, Guido ;

Perrotti, Danilo .

JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (10) :4144-4157

[60] The Diadenosine Homodinucleotide P18 Improves In Vitro Myelination in Experimental Charcot-Marie-Tooth Type 1A [J].

Nobbio, Lucilla ;

Visigalli, Davide ;

Mannino, Elena ;

Fiorese, Fulvia ;

Kassack, Matthias U. ;

Sturla, Laura ;

Prada, Valeria ;

De Flora, Antonio ;

Zocchi, Elena ;

Bruzzone, Santina ;

Schenone, Angelo .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2014, 115 (01) :161-167

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