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Charcot–Marie–Tooth type 4B demyelinating neuropathy: deciphering the role of MTMR phosphatases

Published online by Cambridge University Press:  20 September 2007

Stefano C. Previtali ,
Angelo Quattrini  and
Alessandra Bolino
Stefano C. Previtali
Affiliation:
Neuropathology Unit, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy. INSPE, Institute for Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Angelo Quattrini
Affiliation:
Neuropathology Unit, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy. INSPE, Institute for Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Alessandra Bolino*
Affiliation:
INSPE, Institute for Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy. Dulbecco Telethon Institute, San Raffaele Scientific Institute, Milan, Italy.
*
*Corresponding author: Alessandra Bolino, Dulbecco Telethon Institute and INSPE, Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy. Tel: +39 02 26364743; Fax: +39 02 26434767; E-mail: bolino.alessandra@hsr.it
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Abstract

Charcot–Marie–Tooth type 4B (CMT4B) is a severe autosomal recessive neuropathy with demyelination and myelin outfoldings of the nerve. This disorder is genetically heterogeneous, but thus far, mutations in myotubularin-related 2 (MTMR2) and MTMR13 genes have been shown to underlie CMT4B1 and CMT4B2, respectively. MTMR2 and MTMR13 belong to a family of ubiquitously expressed proteins sharing homology with protein tyrosine phosphatases (PTPs). The MTMR family, which has 14 members in humans, comprises catalytically active proteins, such as MTMR2, and catalytically inactive proteins, such as MTMR13. Despite their homology with PTPs, catalytically active MTMR phosphatases dephosphorylate both PtdIns3P and PtdIns(3,5)P2 phosphoinositides. Thus, MTMR2 and MTMR13 may regulate vesicular trafficking in Schwann cells. Loss of these proteins could lead to uncontrolled folding of myelin and, ultimately, to CMT4B. In this review, we discuss recent findings on this interesting protein family with the main focus on MTMR2 and MTMR13 and their involvement in the biology of Schwann cell and CMT4B neuropathies.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 25 , September 2007 , pp. 1 - 16
Copyright
Copyright © Cambridge University Press 2007

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References

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Further reading, resources and contacts

This following excellent publication comprises interesting chapters on the structure of the myelinated axon; cell biology of myelin assembly; the transport, assembly and functions of myelin lipids; inherited neuropathies; and models of Charcot–Marie–Tooth disease:

Lazzarini, R.A. (2004) Myelin biology and disorders. Vols 1 and 2. Elsevier Academic PressGoogle Scholar
http://www.molgen.ua.ac.be/CMTMutations/default.cfmGoogle Scholar
http://www.neuro.wustl.edu/neuromuscular/time/hmsn.htmlGoogle Scholar
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIMGoogle Scholar