MYO10 · Role of Myosin-X in filopodia elongation and axon guidance
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-10-01 → 2008-09-30
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - MYO10 (Role of Myosin-X in filopodia elongation and axon guidance)
Migrating cells often probe their environment using thin extensions called filopodia. The way filopodia sense other molecules in their immediate surrounding and the way they relay this information to the cell to allow appropriate response to its environment is not clear despite decades of research. Recently Myosin-X has been shown to specifically localize at the tip of filopodia. Myosin-X is a member of a family of proteins called Myosins known to shuttle other molecules within the cell and thus allow their localization at the place where they are required. It is thus possible that Myosin-X shuttles molecules from the tip to the centre of the cell thus un-abling filopodia to communicate with the rest of the cell about what is detected in its environment. To elucidate the role Myosin-X plays in filopodia, we have started a study of its movements within filopodia in relation to other molecules or to small vesicles. We have found that it is unlikely that Myosin-X interacts with vesicules within filopodia. We have also found that Myosin-X accumulated at filopodia tips is aggregated in a complex which, upon some yet unknown trigger, flows back towards the center of the cell. Attachment of Myosin-X to filaments of a molecule called actin which forms a sort of conveying belt within filopodia, is necessary for the movement of Myosin-X complexes towards the cell centre but this movement is strongly regulated by the part of Myosin-X which does not attach to actin but instead binds other molecules. The presence of Myosin-X at filopodia tips is strongly correlated to the attachment of filopodia to its surrounding, potentially helping filopodia communicate with their environment and helping the cells to migrate. The process of cell migration is at the core of many important processes in biology like cancer spreading, embryonic development, nerve growth and regeneration, immunity
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden
Links
Data: CORDIS, © European Union