Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

MTM1 and MTMR2 myotubularins: biochemical activity and the regulation of membrane trafficking in health and disease

Project Coordinator

Fondazione Centro San Raffaele del Monte Tabor DIBIT


Jocelyn Laporte IGBMC-ISERM U596 - UMR7104 Université Louis Pasteur Department of Molecular Biology Illkrich, France
Mikael Simons Department of Neurology University of Göttingen Göttingen, Germany

Myotubularins (MTMs) define a large family of proteins with several members mutated in different neuromuscular disorders: demyelinating Charcot-Marie-Tooth (CMT) type 4B neuropathies (MTMR2 and MTMR13) and congenital myotubular/centronuclear myopathy (MTM1). These rare diseases are characterized by early onset and abnormal myelination or disorganization of skeletal muscle fibers, respectively. MTM1 and MTMR2 are phospholipid phosphatases acting on PtdIns3P and PtdIns(3,5)P2, known to regulate membrane trafficking. Partners 1 and 2 of this network have previously validated genetic in vitro and in vivo models of the diseases, and they identified several interactors, which have been extensively explored. Despite these findings, however, the cellular events regulated by MTM1 and MTMR2 and whether the phosphatase activity mediates MTM1 and MTMR2 biological function still remain to be clarified. To this aim, we propose:

1) to investigate the MTM1 and MTMR2 sub-cellular localization and dynamics using live

cell imaging analysis;

2) to assess whether MTM1 and MTMR2 regulates endosomal membrane trafficking, as

suggested by recent findings of partners 1 and 2;

3) to assess the role of the MTM1 and MTMR2 biochemical activity by exploring functional interaction and phenotypic rescue with phosphatases and kinases involved in the PtdIns3P and PtdIns(3,5)P2 metabolism.

The three Partners of this network gather the necessary expertises on phospholipid metabolism, muscle and myelination pathology, and on the cell biology of membrane trafficking (Partner 3). This project should lead to a better understanding of the pathological mechanisms of these diseases and reveal a common cellular pathway.


E-Rare 2012 - Created by Toussaint Biger