Publication Date:
2010-05-08
Description:
The thickness of the myelin sheath that insulates axons is fitted for optimal nerve conduction velocity. Here, we show that, in Schwann cells, mammalian disks large homolog 1 (Dlg1) interacts with PTEN (phosphatase and tensin homolog deleted on chromosome 10) to inhibit axonal stimulation of myelination. This mechanism limits myelin sheath thickness and prevents overmyelination in mouse sciatic nerves. Removing this brake results also in myelin outfoldings and demyelination, characteristics of some peripheral neuropathies. Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cotter, Laurent -- Ozcelik, Murat -- Jacob, Claire -- Pereira, Jorge A -- Locher, Veronica -- Baumann, Reto -- Relvas, Joao B -- Suter, Ueli -- Tricaud, Nicolas -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1415-8. doi: 10.1126/science.1187735. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cell Biology, Department of Biology, Eidgenossische Technische Hochschule (ETH) Zurich, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448149" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/genetics/*metabolism
;
Animals
;
Axons/physiology
;
Coculture Techniques
;
Ganglia, Spinal/cytology
;
Membrane Proteins/genetics/*metabolism
;
Mice
;
Mice, Inbred C57BL
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Myelin Sheath/*physiology/ultrastructure
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Nerve Tissue Proteins/genetics/*metabolism
;
Neural Conduction
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Neuregulin-1/metabolism
;
PTEN Phosphohydrolase/*metabolism
;
Proto-Oncogene Proteins c-akt/metabolism
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RNA Interference
;
Rats
;
Schwann Cells/*physiology
;
Sciatic Nerve/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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