Myosin 1-mediated Exocytosis of Glucose Transporter Storage Vesicles

• Applicant: Professor Dr. Dietmar J. Manstein
• Subject Area: Structural Biology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228080467

The project aims at a better understanding of myosin 1-dependent mechanisms underlying the exocytosis of glucose transporter storage vesicles. We will examine the role of Myo1c and Myo1b in the trafficking of glucose transporter 4 loaded vesicles and links between signalling events and the vesicle-trafficking machinery in adipocytes and myocyte. The characterisation of the cytoplasmic, actin-based motor protein Myo1c and its regulated interaction with partner proteins in adipocytes are at the heart of our work program. We propose a mechanism by which PKA-mediated phosphorylation of the Myo1c neck region and the ensuing replacement of calmodulin at IQ1 by 14-3-3 leads to the formation of activated Myo1c dimers, promotes specific interactions with phosphoproteins such as kinesin-1. Additionally, replacement of calmodulin at IQ1 by 14-3-3 is predicted to disrupt the Ca2+-sensitive interactions of Myo1c monomers with the 192 kDa phosphoprotein Rictor, a binding partner of the large protein kinase mTOR. We will examine the role and interaction partners of Myo1b in myocytes and extend our studies to the role of myosin 1-dependent process in the uptake of glucose by specific types of cancer cells.

• DFG Programme: Research Grants