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Novel mechanism controlling cell migration and endocytosis

A team led by Dr Matthias Krause, Randall Division of Cell & Molecular Biophysics, King’s College London, demonstrated in a paper published in the Journal of Cell Biology, that Lamellipodin binds to the Scar/WAVE protein complex, a known mediator of cell migration. However, it was enigmatic how the Scar/WAVE protein complex is regulated to control cell migration in vivo.

Importantly, this study showed that Lamellipodin regulates cell migration via the Scar/WAVE complex, both at the level of the individual cell as well as in processes taking place in vivo that rely on tightly coordinated movement of cell populations. These included the migration of cells during embryonic development (pigment cell precursors (melanoblasts) during mouse development, neural crest cell migration in the frog embryo and border cell migration in fruit fly larvae). 

During development and cancer progression, cells in the human body migrate towards signals send out by other cells. The cells sense these signals by using ‘antenna’ on their surface, which are called receptors. One of the most important receptors is the epidermal growth factor receptor. Cells reduce the number of receptors on their surface by taking them up into the cell into small vesicles (a process called endocytosis). 

 

In another paper recently published in The EMBO Journal, Dr Krause and his team discovered that Lamellipodin regulates the uptake (endocytosis) of the epidermal growth factor receptor. They demonstrated that another protein called endophilin brings Lamellipodin to the site where the receptors are taken up. Lamellipodin in turn recruits a protein called Mena, which then helps to cleave off the forming vesicle containing the receptors. 

Taken together, both studies identify Lamellipodin as an essential regulator of normal cell migration and uptake of receptors, highlighting the need to examine its function during cancer progression. 

This work was funded by the Wellcome Trust, Royal Society, and BBSRC. 

Ah-Lai Law, Anne Vehlow, Maria Kotini, Lauren Dodgson, Daniel Soong, Eric Theveneau, Cristian Bodo, Eleanor Taylor, Christel Navarro, Upamali Perera, Magdalene Michael, Graham A. Dunn, Daimark Bennett, Roberto Mayor, and Matthias Krause (2013) Lamellipodin and the Scar/WAVE complex cooperate to regulate cell migration in vivo. Journal of Cell Biology, Journal of Cell Biology 203(4), 673-689. 

View the paper published in the Journal of Cell Biology  

View the Journal of Cell Biology's 'In Focus' feature on the paper

Anne Vehlow, Daniel Soong, Gema Vizcay-Barrena, Cristian Bodo, Ah-Lai Law, Upamali Perera, and Matthias Krause (2013) Endophilin and Lamellipodin Cooperate to Regulate F-actin-dependent Endocytosis of the EGF-receptor. EMBO J 32, 2722-2734. 

View the EMBO Journal 

Find out more about the Krause Group's research