Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end-plate innervation.

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_07FE1A3D3EC7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end-plate innervation.
Journal
Glia
Author(s)
Bouçanova F., Pollmeier G., Sandor K., Morado Urbina C., Nijssen J., Médard J.J., Bartesaghi L., Pellerin L., Svensson C.I., Hedlund E., Chrast R.
ISSN
1098-1136 (Electronic)
ISSN-L
0894-1491
Publication state
Published
Issued date
01/2021
Peer-reviewed
Oui
Volume
69
Number
1
Pages
124-136
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Recent studies in neuron-glial metabolic coupling have shown that, in the CNS, astrocytes and oligodendrocytes support neurons with energy-rich lactate/pyruvate via monocarboxylate transporters (MCTs). The presence of such transporters in the PNS, in both Schwann cells and neurons, has prompted us to question if a similar interaction may be present. Here we describe the generation and characterization of conditional knockout mouse models where MCT1 or MCT4 is specifically deleted in Schwann cells (named MCT1 and MCT4 cKO). We show that MCT1 cKO and MCT4 cKO mice develop normally and that myelin in the PNS is preserved. However, MCT1 expressed by Schwann cells is necessary for long-term maintenance of motor end-plate integrity as revealed by disrupted neuromuscular innervation in mutant mice, while MCT4 appears largely dispensable for the support of motor neurons. Concomitant to detected structural alterations, lumbar motor neurons from MCT1 cKO mice show transcriptional changes affecting cytoskeletal components, transcriptional regulators, and mitochondria related transcripts, among others. Together, our data indicate that MCT1 plays a role in Schwann cell-mediated maintenance of motor end-plate innervation thus providing further insight into the emerging picture of the biology of the axon-glia metabolic crosstalk.
Keywords
Animals, Mice, Monocarboxylic Acid Transporters/genetics, Motor Endplate, Muscle Proteins, Myelin Sheath, Schwann Cells, Symporters/genetics, PNS, RNA-Seq, Schwann cell, monocarboxylate transporter, motor neuron
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2020 13:09
Last modification date
22/07/2022 5:37
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