In migrating cells, the establishment of planar cell polarity (PCP) must be synchronised with the remodelling of the extracellular matrix (ECM). Indeed, previous studies have shown that PCP is linked with dynamic ECM modifications. But do proteins that are involved in establishing PCP in migrating cells have an active in role in ECM degradation and remodelling? On page , Jason Jessen and colleagues now provide an answer by highlighting a role for the PCP protein Vang-like 2 (VANGL2) in the trafficking of membrane type-1 matrix metalloproteinase (MMP14 or MT1-MMP). Biotinylation and antibody-uptake assays reveal that siRNA-mediated knockdown of VANGL2 impairs MMP14 endocytosis and increases the levels of the protease on the cell surface. Furthermore, focal adhesion kinase (FAK) acts downstream of VANGL2 in the regulation of MMP14 endocytosis. Using trilobite/vangl2 zebrafish mutants, the researchers confirm that Vangl2 controls Mmp14 activity at the cell surface by regulating endocytosis of the enzyme. Loss of Vangl2 leads to increased ECM degradation and a strong convergence and extension phenotype during gastrulation. The authors propose a model whereby asymmetrical Vangl2 distribution in polarised cells promotes Mmp14 activity on specific cell surfaces to allow localised ECM degradation and targeted migration.
