Model for the function of the Protrudin pathway in invadopodia formation and exocytosis of MT1-MMP. When the Protrudin pathway is active (right), the ER protein Protrudin makes contact sites with RAB7 and phosphatidylinositol 3-phosphate(PI3P)–positive LE/Lys, which contain MT1-MMP. In the ER–LE/Lys contact sites, the microtubule motor kinesin-1 is handed over from Protrudin to the RAB7-binding kinesin-1 adaptor protein FYCO1. This enables the translocation of the LE/Lys along microtubules toward immature invadopodia at the plasma membrane. SYT7-dependent fusion of LE/Lys with the invadopodial plasma membrane provides membrane for the maturing invadopodia and ensures that MT1-MMP is exposed at the cell surface. This enables invadopodia growth and degradation of the ECM and facilitates cell invasion. Upon depletion of any of the components of the Protrudin pathway (left), MT1-MMP–containing LE/Lys cluster perinuclearly. This prevents MT1-MMP exocytosis, invadopodia maturation, and cell invasion. MTOC, microtubule organizing center.