CMT 4B demyelinating neuropathy: deciphering the role of MTMR phosphatases

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Expert Rev Mol Med. 2007 Sep 20;9(25):1-16.

Charcot-Marie-Tooth type 4B demyelinating neuropathy: deciphering

the role of MTMR phosphatases.

Previtali SC, Quattrini A, Bolino A.

INSPE, Institute for Experimental Neurology, San Raffaele Scientific

Institute, Milan, Italy.

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.