Dynamin 2 mechanoenzyme is a key regulator of membrane remodeling and gain-of-function mutations in its gene cause centronuclear myopathies. Here, we investigate the functions of dynamin 2 isoforms ...and their associated phenotypes and, specifically, the ubiquitous and muscle-specific dynamin 2 isoforms expressed in skeletal muscle. In cell-based assays, we show that a centronuclear myopathy-related mutation in the ubiquitous but not the muscle-specific dynamin 2 isoform causes increased membrane fission. In vivo, overexpressing the ubiquitous dynamin 2 isoform correlates with severe forms of centronuclear myopathy, while overexpressing the muscle-specific isoform leads to hallmarks seen in milder cases of the disease. Previous mouse studies suggested that reduction of the total dynamin 2 pool could be therapeutic for centronuclear myopathies. Here, dynamin 2 splice switching from muscle-specific to ubiquitous dynamin 2 aggravated the phenotype of a severe X-linked form of centronuclear myopathy caused by loss-of-function of the MTM1 phosphatase, supporting the importance of targeting the ubiquitous isoform for efficient therapy in muscle. Our results highlight that the ubiquitous and not the muscle-specific dynamin 2 isoform is the main modifier contributing to centronuclear myopathy pathology.
A series of 2,3-diphenylbuta-1,3-dienes (DPBs) bearing thiophene (
T-DPB
), bithiophene (
BT-DPB
) and ethylenedioxythiophene (
EDOT-DPB
) electropolymerizable units were prepared through ...desilylation reactions of the corresponding 3,4-diphenylsilole derivatives. These DPB derivatives exhibit remarkably different aggregation induced emission (AIE) or aggregation enhanced emission (AEE) behaviour depending on the strength of the molecular interactions occurring in the solid state. Indeed,
T-DPB
and
EDOT-DPB
were found to be good AIEgens while
BT-DPB
exhibited AEE behaviour. Finally, the electrochemical properties of these new materials were investigated revealing for all DPBs the occurrence of electropolymerization processes leading potentially to low band gap polymers.
Electropolymerizable diphenylbuta-1,3-diene derivatives with AIE or AEE properties were synthesized allowing low bandgap polymers to be obtained through electropolymerization processes.
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