Understanding the Role of Motors in Subcellular Mechanics of Organelles by Controlling Myo6-Cargo Interactions in situ

Project Information

MELANCHOR

Grant agreement ID: 797150

DOI

10.3030/797150

Project terminated on 20 August 2019

EC signature date 26 March 2018

Start date 1 April 2018

End date 31 March 2020

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 185 076,00

EU contribution

€ 185 076,00

Coordinated by

INSTITUT CURIE
France

Periodic Reporting for period 1 - MELANCHOR (Understanding the Role of Motors in Subcellular Mechanics of Organelles by Controlling Myo6-Cargo Interactions in situ)

Reporting period: 2018-04-01 to 2020-03-31

Summary of the context and overall objectives of the project

"Cells in the body use motor forces to deliver materials to their destination, whether outside the cell for materials involved in maintaining tissues, or inside the cell for use in feeding or recycling. Molecular motor proteins, such as Myosin VI, play critical roles in ""packing"" or ""unpacking"" materials from their packaging in lipid membranes. Seeing how these routine activities happen at the level of individual molecules is important for understanding how our bodies grow, develop, and perform basic functions such as digesting food and disposing of waste. It is also critical to understanding disease states, including neurodegenerative diseases that involve failures to dispose of waste products, or cancer that involves uncontrolled growth of the cancer cell. The overall objectives of this project were to discover how a molecular motor, Myosin VI, influences the processing of lipid membrane compartments and how this motor generates force at the level of individual molecules in the cell."

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The researchers worked at Institut Curie (Paris, France) to understand how Myosin VI controls the manufacturing of skin pigment granules (melanin). Melanin is manufactured in microscopic compartments enclosed in lipid membranes. The researchers used microscopes and genetic mutations to study how Myosin VI finds these compartments and how it is able to exert motor force. They found a unique mutation controls both the ability of Myosin VI to find melanin compartments and the exert motor force there. They also found ways to skip this step that controls the Myosin VI motor, which increased the amount of the motor present, and (in the opposite direction) to prevent the motor from being able to exert force anywhere. These results show how Myosin VI might be controlled in other situations, such as processing nutrients or recycling of cell components, not only in the making of melanin.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The findings show that molecular motors such as Myosin VI play important roles not only in transporting materials in cells (as was previously known), but also in using motor force to pack or unpack these materials. The findings also provide proof-of-concept for methods to activate or inactivate the Myosin VI motor. These findings create new opportunities for applied research into how Myosin VI could be controlled using drugs to increase or decrease its availability or its motor force. These findings are relevant to understanding how Myosin VI contributes to disease states such as cancer, and how drugs could be used to fight disease by controlling how Myosin VI behaves in the body.

Mutant Myo6 that is not present at melanosomes also fails to support normal pigment turnover.