CMT 4B1 + B2: Myotubularin-Related (MTMR) Phospholipid Phosphatase Proteins in t

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Mol Neurobiol. 2007 Jun;35(3):308-16.

Myotubularin-Related (MTMR) Phospholipid Phosphatase Proteins in the

Peripheral Nervous System.

Bolis A, Zordan P, Coviello S, Bolino A.

San Raffaele Scientific Institute, Dulbecco Telethon Institute,

Milan, Italy.

Myotubularin-related proteins (MTMRs) constitute a broad family of

ubiquitously expressed phosphatases with 14 members in humans, of

which eight are catalytically active phosphatases, while six are

catalytically inactive. Active MTMRs possess 3-phosphatase activity

toward both PtdIns3P and PtdIns(3, 5)P 2 poliphosphoinositides

(PPIn), suggesting an involvement in intracellular trafficking and

membrane homeostasis. Among MTMRs, catalytically active MTMR2 and

inactive MTMR13 have a nonredundant function in nerve.

Loss of either MTMR2 or MTMR13 causes Charcot-Marie-Tooth type 4B1

and B2 neuropathy, respectively, characterized by demyelination and

redundant loops of myelin known as myelin outfoldings. In Mtmr2-null

mouse nerves, these aberrant foldings occur at 3-4 weeks after

birth, a time when myelination is established, and Schwann cells are

still elongating to reach the final internodal length.

Moreover, Mtmr2-specific ablation in Schwann cells is both

sufficient and necessary to provoke CMT4B1 with myelin outfoldings.

MTMR2 phospholipid phosphatase might regulate intracellular

trafficking events and membrane homeostasis in Schwann cells during

postnatal nerve development. In this review, we will discuss recent

findings on the MTMR family with a major focus on MTMR2 and MTMR13

and their putative role in Schwann cell biology.