Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling
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Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling. / Schulz, Alexander; Kyselyova, Anna; Baader, Stephan L; Jung, Marie Juliane; Zoch, Ansgar; Mautner, Victor-Felix; Hagel, Christian; Morrison, Helen.
In: BRAIN, Vol. 137, No. 2, 01.02.2014, p. 420-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling
AU - Schulz, Alexander
AU - Kyselyova, Anna
AU - Baader, Stephan L
AU - Jung, Marie Juliane
AU - Zoch, Ansgar
AU - Mautner, Victor-Felix
AU - Hagel, Christian
AU - Morrison, Helen
PY - 2014/2/1
Y1 - 2014/2/1
N2 - Axonal surface proteins encompass a group of heterogeneous molecules, which exert a variety of different functions in the highly interdependent relationship between axons and Schwann cells. We recently revealed that the tumour suppressor protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type 2, impacts significantly on axon structure maintenance in the peripheral nervous system. We now report on a role of neuronal merlin in the regulation of the axonal surface protein neuregulin 1 important for modulating Schwann cell differentiation and myelination. Specifically, neuregulin 1 type III expression is reduced in sciatic nerve tissue of neuron-specific knockout animals as well as in biopsies from seven patients with neurofibromatosis type 2. In vitro experiments performed on both the P19 neuronal cell line and primary dorsal root ganglion cells demonstrate the influence of merlin on neuregulin 1 type III expression. Moreover, expression of ERBB2, a Schwann cell receptor for neuregulin 1 ligands is increased in nerve tissue of both neuron-specific merlin knockout animals and patients with neurofibromatosis type 2, demonstrating for the first time that axonal merlin indirectly regulates Schwann cell behaviour. Collectively, we have identified that neuronally expressed merlin can influence Schwann cell activity in a cell-extrinsic manner.
AB - Axonal surface proteins encompass a group of heterogeneous molecules, which exert a variety of different functions in the highly interdependent relationship between axons and Schwann cells. We recently revealed that the tumour suppressor protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type 2, impacts significantly on axon structure maintenance in the peripheral nervous system. We now report on a role of neuronal merlin in the regulation of the axonal surface protein neuregulin 1 important for modulating Schwann cell differentiation and myelination. Specifically, neuregulin 1 type III expression is reduced in sciatic nerve tissue of neuron-specific knockout animals as well as in biopsies from seven patients with neurofibromatosis type 2. In vitro experiments performed on both the P19 neuronal cell line and primary dorsal root ganglion cells demonstrate the influence of merlin on neuregulin 1 type III expression. Moreover, expression of ERBB2, a Schwann cell receptor for neuregulin 1 ligands is increased in nerve tissue of both neuron-specific merlin knockout animals and patients with neurofibromatosis type 2, demonstrating for the first time that axonal merlin indirectly regulates Schwann cell behaviour. Collectively, we have identified that neuronally expressed merlin can influence Schwann cell activity in a cell-extrinsic manner.
KW - Adult
KW - Aged
KW - Animals
KW - Cell Line
KW - Cells, Cultured
KW - Female
KW - Humans
KW - Male
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Middle Aged
KW - Neuregulin-1
KW - Neurofibromatosis 2
KW - Neurofibromin 2
KW - Neurons
KW - Receptor, erbB-2
KW - Schwann Cells
KW - Signal Transduction
U2 - 10.1093/brain/awt327
DO - 10.1093/brain/awt327
M3 - SCORING: Journal article
C2 - 24309211
VL - 137
SP - 420
EP - 432
JO - BRAIN
JF - BRAIN
SN - 0006-8950
IS - 2
ER -