Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.

Andrea Toledo, Elena Grieger, Khalad Karram, Helen Morrison, Stephan L. Baader
PLoS ONE. 2018-05-01; 13(5): e0196726
DOI: 10.1371/journal.pone.0196726

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1. PLoS One. 2018 May 1;13(5):e0196726. doi: 10.1371/journal.pone.0196726.
eCollection 2018.

Neurofibromatosis type 2 tumor suppressor protein is expressed in
oligodendrocytes and regulates cell proliferation and process formation.

Toledo A(1)(2), Grieger E(1), Karram K(3), Morrison H(4), Baader SL(1).

Author information:
(1)Institute of Anatomy, Anatomy and Cell Biology, Bonn, Germany.
(2)Laboratorio de Cultivo de Tejidos, Sección Biología Celular, Facultad de
Ciencias, UdelaR, Montevideo, Uruguay.
(3)Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz,
Germany.
(4)Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany.

The neurofibromatosis type 2 (NF2) tumor suppressor protein Merlin functions as a
negative regulator of cell growth and actin dynamics in different cell types
amongst which Schwann cells have been extensively studied. In contrast, the
presence and the role of Merlin in oligodendrocytes, the myelin forming cells
within the CNS, have not been elucidated. In this work, we demonstrate that
Merlin immunoreactivity was broadly distributed in the white matter throughout
the central nervous system. Following Merlin expression during development in the
cerebellum, Merlin could be detected in the cerebellar white matter tract at
early postnatal stages as shown by its co-localization with Olig2-positive cells
as well as in adult brain sections where it was aligned with myelin basic protein
containing fibers. This suggests that Merlin is expressed in immature and mature
oligodendrocytes. Expression levels of Merlin were low in oligodendrocytes as
compared to astrocytes and neurons throughout development. Expression of Merlin
in oligodendroglia was further supported by its identification in either
immortalized cell lines of oligodendroglial origin or in primary oligodendrocyte
cultures. In these cultures, the two main splice variants of Nf2 could be
detected. Merlin was localized in clusters within the nuclei and in the
cytoplasm. Overexpressing Merlin in oligodendrocyte cell lines strengthened
reduced impedance in XCELLigence measurements and Ki67 stainings in cultures over
time. In addition, the initiation and elongation of cellular projections were
reduced by Merlin overexpression. Consistently, cell migration was retarded in
scratch assays done on Nf2-transfected oligodendrocyte cell lines. These data
suggest that Merlin actively modulates process outgrowth and migration in
oligodendrocytes.

DOI: 10.1371/journal.pone.0196726
PMCID: PMC5929554
PMID: 29715273 [Indexed for MEDLINE]


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