The interaction of amphiphysin 2 (encoded by the BIN1 gene) and dynamin 2 (encoded by the DNM2 gene) is necessary for membrane fission:
- amphiphysin 2 triggers the formation of the membrane tubule by inducing membrane bending;
- dynamin 2 binds to amphiphysin 2 and then causes tubule fission.
Overexpression of BIN1 leads to :
- an improvement in muscle atrophy and key histopathological features in mouse models of moderate DNM2-related centronuclear myopathy;
- an improvement in perinatal mortality and survival of mice with more severe forms.
Amphiphysin 2 is thought to act as a regulator of the fission action of dynamin 2, which is increased with mutation/gain of function in DNM2-related centronuclear myopathy.
As in myotubular myopathy, overexpression of BIN1 appears to be a therapeutic option for DNM2-related centronuclear myopathy.
