Mtmr2, or myotubularin-related protein 2, is a ubiquitously expressed phosphatase. Its preferred substrate is phosphatidylinositol (3,5)-biphosphate, a regulator of membrane homeostasis and vesicle transport. MTMR2 is implicated in multiple biological processes and is associated with pathways such as the IFNγ/STAT1/IRF1 pathway [1]. It plays a crucial role in normal physiological functions and its study benefits from genetic models like knockout mouse models for understanding its functions.

Disruption of Mtmr2 in mice leads to a CMT4B1-like neuropathy with myelin outfolding, predominantly at paranodal myelin, and impaired spermatogenesis, resulting in azoospermia [2]. In Schwann cells, loss of Mtmr2-Dlg1 interaction may dysregulate membrane homeostasis in the paranodal region, causing myelin abnormalities [2]. Also, in Mtmr2-null mice, altered levels of the critical signalling protein AKT are observed, suggesting that Mtmr2 plays a role in cellular signalling processes [3].

In conclusion, Mtmr2 is essential for maintaining normal membrane homeostasis, especially in the context of myelin formation in the peripheral nervous system and spermatogenesis. The study of Mtmr2 knockout mouse models has provided insights into its role in Charcot-Marie-Tooth type 4B1 neuropathy and related physiological disruptions, highlighting its significance in understanding these disease conditions.

References:

1. Jiang, Lei, Liu, Jun-Yan, Shi, Yan, Cui, You-Hong, Yu, Pei-Wu. 2019. MTMR2 promotes invasion and metastasis of gastric cancer via inactivating IFNγ/STAT1 signaling. In Journal of experimental & clinical cancer research : CR, 38, 206. doi:10.1186/s13046-019-1186-z. https://pubmed.ncbi.nlm.nih.gov/31113461/

2. Bolino, Alessandra, Bolis, Annalisa, Previtali, Stefano Carlo, Quattrini, Angelo, Wrabetz, Lawrence. . Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis. In The Journal of cell biology, 167, 711-21. doi:. https://pubmed.ncbi.nlm.nih.gov/15557122/

3. Berger, Philipp, Tersar, Kristian, Ballmer-Hofer, Kurt, Suter, Ueli. . The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling. In Journal of cellular and molecular medicine, 15, 307-15. doi:10.1111/j.1582-4934.2009.00967.x. https://pubmed.ncbi.nlm.nih.gov/19912440/