Cell migration is a complex process that is central to many aspects of medicine and biological research: embryo development, tumour development (invasiveness and vascularization), and nerve regeneration after injury and stem cell migration. Migrating cells heavily rely on their ability to adhere to and extract information from extracellular molecules. For this purpose, they extend thin protrusions (filopodia) that probe the environment ahead of the cell. Due to fixation artefacts, these very thin and motile structures have proved difficult to analyse. Recent live cell imaging techniques offer new tools to elucidate how they form and understand their function. Integrins are transmembrane receptors of the extracellular matrix and regulate adhesion and migration by relaying external signals to the cytoskeleton. In neurons, integrins are also involved in several aspects of axon growth and guidance. Myosin-X (Myo10) was recently identified as an integrin-binding partner. Myo10 is a unique motor protein in that it not only binds to actin, but it also interacts with microtubules and several signalling molecules that are heavily involved in cell migration. Myo10 is found at the tip of filopodia and it influences their length and number. Interestingly, Myo10 is strongly expressed in neurons at the growth cone, the sensing tip of axons.
This project is aimed at answering the following questions:
- What role does Myo10 play in filopodia elongation? The implication of a possible vesicle docking and delivery function of Myo10 and the involvement of integrins will be assessed.
- What role does Myo10 play in axon growth and guidance? Manipulation of Myo10 expression and its binding to integrins will be carried out in live neuroblastoma cells.
Advanced live cell imaging techniques will be used to dissect the molecular mechanisms implicated. Answers to these questions will help understand cell migration and have potential applications in both tumour biology and neuroscience.
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