TY - JOUR T1 - GGA2 and RAB13 regulate activity-dependent β1-integrin recycling JF - bioRxiv DO - 10.1101/353086 SP - 353086 AU - Pranshu Sahgal AU - Jonna Alanko AU - Ilkka Paatero AU - Antti Arjonen AU - Mika Pietilä AU - Anne Rokka AU - Johanna Ivaska Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/06/22/353086.abstract N2 - β1-integrins mediate cell-matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes like cancer cell invasion. Here we employ unbiased RNAi screening to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin and its role in recycling of the active but not inactive β1-integrins. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion congruent with its ability to regulate the dynamics of active integrins. Using the proximity-dependent biotin identification (BioID) method, we identify two RAB family small GTPases, RAB13 and RAB10, associating with GGA2 and β1-integrin. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, identically to GGA2 depletion, indicating that both facilitate recycling of active β1-integrins to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic. ER -