(mentions CMT X) The myotubularin family of lipid phosphatases in disease and in

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Biochem J. 2010 Dec 22;433(2):253-262.

The myotubularin family of lipid phosphatases in disease and in spermatogenesis.

Mruk DD, Cheng CY.

Center for Biomedical Research, Population Council, 1230 York Avenue, New York,

NY 10065, U.S.A.

Abstract

The MTM (myotubularin)/MTMR (myotubularin-related) protein family is comprised

of 15 lipid phosphatases, of which nine members are catalytically active. MTMs

are known to play a fundamental role in human physiology as gene mutations can

give rise to X-linked myotubular myopathy or Charcot-Marie-Tooth disease, which

manifest in skeletal muscle or in peripheral neurons respectively.

Interestingly, studies have shown MTMR2 and MTMR5, two MTM family members, to be

highly expressed in the testis, particularly in Sertoli and germ cells, and

knockout of either gene resulted in spermatogenic defects.

Other studies have shown that MTMR2 functions in endocytosis and membrane

trafficking. In the testis, MTMR2 interacts and co-localizes with

c-Src/phospho-Src

-(Tyr416), a non-receptor protein tyrosine kinase that regulates the

phosphorylation state of proteins at the apical ES (ectoplasmic specialization),

a unique type of cell junction found between Sertoli cells and

elongating/elongated spermatids. In the present review, we highlight recent

findings that have made a significant impact on our understanding of this

protein family in normal cell function and in disease, with the emphasis on the

role of MTMs and MTMRs in spermatogenesis.

We also describe a working model to explain how MTMR2 interacts with other

proteins such as c-Src, dynamin 2, EPS8 (growth factor receptor pathway

substrate 8) and ARP2/3 (actin-related protein 2/3) at the apical ES and the

apical TBC (tubulobulbar complex; tubular-like invaginations that function in

the disassembly of the apical ES and in the recycling of its components) to

regulate spermiation at late stage VIII of the seminiferous epithelial cycle.