Volker Haucke is the head of the Department for Molecular Pharmacology and Cell Biology at the Leibnitz Institut für Molekulare Phamakologie in Berlin, Germany. The research focus of the Haucke lab is the uptake into cells and the transport within cells of various substances. In this interdisciplinary team molecular biologists work together with biochemists, geneticists and physicists to decipher the pathways in cells and thus to discover the causes of diseases like e. g. CNM. For that purpose, high resolution imaging methods, esp. fluorescence and electron microscopy are linked with chemical and biochemical methods and experiments in animal models. Recent works of Katharina Ketel from his lab and Jocelyn Laportes working group in Strasbourg revealed, that mutations in the MTM1-gene (responsible for myotubular myopathy) leads to malfunctions in the transport of certain proteins to the cell membrane, as e. g. the so-called integrines which are important for the muscle performance (picture 1) . The MTM1 encoded enzyme (myotubularine) does not operate alone but together with another one as part of a dynamic machinery to recycle proteins. Exactly this recycling seems not to work properly in CNM patients. Interestingly, the treatment of cells with a MTM1 gen defect with a novel agent could reestablish the malfunctioning protein transport. Future studies will reveal whether and to what extent similar approaches can be used as therapy for CNM in patients.
Picture 1: Accumulation of Integrine (red), an important component in muscles, in Vesicles (green) from cells without MTM1 (images on the right) in comparison to control cells (images on the left).
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Publication on the topic:
Ketel K, Krauss M, Nicot AS, Puchkov D, Wieffer M, Müller R, Subramanian D, Schultz C, Laporte J, Haucke V. (2016) A phosphoinositide conversion mechanism for exit from endosomes. Nature Jan 13 [doi: 10.1038/nature16516] http://www.nature.com/nature/journal/v529/n7586/full/nature16516.html