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SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia

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SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia. / Glerup, Simon; Olsen, Ditte; Vaegter, Christian B; Gustafsen, Camilla; Sjoegaard, Susanne S; Hermey, Guido; Kjolby, Mads; Molgaard, Simon; Ulrichsen, Maj; Boggild, Simon; Skeldal, Sune; Fjorback, Anja N; Nyengaard, Jens R; Jacobsen, Jan; Bender, Dirk; Bjarkam, Carsten R; Sørensen, Esben S; Füchtbauer, Ernst-Martin; Eichele, Gregor; Madsen, Peder; Willnow, Thomas E; Petersen, Claus M; Nykjaer, Anders.

In: NEURON, Vol. 82, No. 5, 04.06.2014, p. 1074-87.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Glerup, S, Olsen, D, Vaegter, CB, Gustafsen, C, Sjoegaard, SS, Hermey, G, Kjolby, M, Molgaard, S, Ulrichsen, M, Boggild, S, Skeldal, S, Fjorback, AN, Nyengaard, JR, Jacobsen, J, Bender, D, Bjarkam, CR, Sørensen, ES, Füchtbauer, E-M, Eichele, G, Madsen, P, Willnow, TE, Petersen, CM & Nykjaer, A 2014, 'SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia', NEURON, vol. 82, no. 5, pp. 1074-87. https://doi.org/10.1016/j.neuron.2014.04.022

APA

Glerup, S., Olsen, D., Vaegter, C. B., Gustafsen, C., Sjoegaard, S. S., Hermey, G., Kjolby, M., Molgaard, S., Ulrichsen, M., Boggild, S., Skeldal, S., Fjorback, A. N., Nyengaard, J. R., Jacobsen, J., Bender, D., Bjarkam, C. R., Sørensen, E. S., Füchtbauer, E-M., Eichele, G., ... Nykjaer, A. (2014). SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia. NEURON, 82(5), 1074-87. https://doi.org/10.1016/j.neuron.2014.04.022

Vancouver

Glerup S, Olsen D, Vaegter CB, Gustafsen C, Sjoegaard SS, Hermey G et al. SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia. NEURON. 2014 Jun 4;82(5):1074-87. https://doi.org/10.1016/j.neuron.2014.04.022

Bibtex

@article{e954e6a8e03b40e183e2a3f41ea23111,
title = "SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia",
abstract = "Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75(NTR). CNS neurons, but not glia, express SorCS2 as a single-chain protein that is essential for proBDNF-induced growth cone collapse in developing dopaminergic processes. SorCS2- or p75(NTR)-deficient in mice caused reduced dopamine levels and metabolism and dopaminergic hyperinnervation of the frontal cortex. Accordingly, both knockout models displayed a paradoxical behavioral response to amphetamine reminiscent of ADHD. Contrary, in PNS glia, but not in neurons, proteolytic processing produced a two-chain SorCS2 isoform that mediated proNT-dependent Schwann cell apoptosis. Sciatic nerve injury triggered generation of two-chain SorCS2 in p75(NTR)-positive dying Schwann cells, with apoptosis being profoundly attenuated in Sorcs2(-/-) mice. In conclusion, we have demonstrated that two-chain processing of SorCS2 enables neurons and glia to respond differently to proneurotrophins.",
keywords = "Animals, Apoptosis, Brain, Brain-Derived Neurotrophic Factor, Corpus Striatum, Dopamine, Dopaminergic Neurons, Frontal Lobe, Growth Cones, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Net, Nerve Tissue Proteins, Neurons, Receptors, Cell Surface, Receptors, Nerve Growth Factor, Schwann Cells, Substantia Nigra, Ventral Tegmental Area",
author = "Simon Glerup and Ditte Olsen and Vaegter, {Christian B} and Camilla Gustafsen and Sjoegaard, {Susanne S} and Guido Hermey and Mads Kjolby and Simon Molgaard and Maj Ulrichsen and Simon Boggild and Sune Skeldal and Fjorback, {Anja N} and Nyengaard, {Jens R} and Jan Jacobsen and Dirk Bender and Bjarkam, {Carsten R} and S{\o}rensen, {Esben S} and Ernst-Martin F{\"u}chtbauer and Gregor Eichele and Peder Madsen and Willnow, {Thomas E} and Petersen, {Claus M} and Anders Nykjaer",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = jun,
day = "4",
doi = "10.1016/j.neuron.2014.04.022",
language = "English",
volume = "82",
pages = "1074--87",
journal = "NEURON",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia

AU - Glerup, Simon

AU - Olsen, Ditte

AU - Vaegter, Christian B

AU - Gustafsen, Camilla

AU - Sjoegaard, Susanne S

AU - Hermey, Guido

AU - Kjolby, Mads

AU - Molgaard, Simon

AU - Ulrichsen, Maj

AU - Boggild, Simon

AU - Skeldal, Sune

AU - Fjorback, Anja N

AU - Nyengaard, Jens R

AU - Jacobsen, Jan

AU - Bender, Dirk

AU - Bjarkam, Carsten R

AU - Sørensen, Esben S

AU - Füchtbauer, Ernst-Martin

AU - Eichele, Gregor

AU - Madsen, Peder

AU - Willnow, Thomas E

AU - Petersen, Claus M

AU - Nykjaer, Anders

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/6/4

Y1 - 2014/6/4

N2 - Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75(NTR). CNS neurons, but not glia, express SorCS2 as a single-chain protein that is essential for proBDNF-induced growth cone collapse in developing dopaminergic processes. SorCS2- or p75(NTR)-deficient in mice caused reduced dopamine levels and metabolism and dopaminergic hyperinnervation of the frontal cortex. Accordingly, both knockout models displayed a paradoxical behavioral response to amphetamine reminiscent of ADHD. Contrary, in PNS glia, but not in neurons, proteolytic processing produced a two-chain SorCS2 isoform that mediated proNT-dependent Schwann cell apoptosis. Sciatic nerve injury triggered generation of two-chain SorCS2 in p75(NTR)-positive dying Schwann cells, with apoptosis being profoundly attenuated in Sorcs2(-/-) mice. In conclusion, we have demonstrated that two-chain processing of SorCS2 enables neurons and glia to respond differently to proneurotrophins.

AB - Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75(NTR). CNS neurons, but not glia, express SorCS2 as a single-chain protein that is essential for proBDNF-induced growth cone collapse in developing dopaminergic processes. SorCS2- or p75(NTR)-deficient in mice caused reduced dopamine levels and metabolism and dopaminergic hyperinnervation of the frontal cortex. Accordingly, both knockout models displayed a paradoxical behavioral response to amphetamine reminiscent of ADHD. Contrary, in PNS glia, but not in neurons, proteolytic processing produced a two-chain SorCS2 isoform that mediated proNT-dependent Schwann cell apoptosis. Sciatic nerve injury triggered generation of two-chain SorCS2 in p75(NTR)-positive dying Schwann cells, with apoptosis being profoundly attenuated in Sorcs2(-/-) mice. In conclusion, we have demonstrated that two-chain processing of SorCS2 enables neurons and glia to respond differently to proneurotrophins.

KW - Animals

KW - Apoptosis

KW - Brain

KW - Brain-Derived Neurotrophic Factor

KW - Corpus Striatum

KW - Dopamine

KW - Dopaminergic Neurons

KW - Frontal Lobe

KW - Growth Cones

KW - HEK293 Cells

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nerve Net

KW - Nerve Tissue Proteins

KW - Neurons

KW - Receptors, Cell Surface

KW - Receptors, Nerve Growth Factor

KW - Schwann Cells

KW - Substantia Nigra

KW - Ventral Tegmental Area

U2 - 10.1016/j.neuron.2014.04.022

DO - 10.1016/j.neuron.2014.04.022

M3 - SCORING: Journal article

C2 - 24908487

VL - 82

SP - 1074

EP - 1087

JO - NEURON

JF - NEURON

SN - 0896-6273

IS - 5

ER -