Abstract
Proper functioning of the precisely controlled endolysosomal system is essential for maintaining the homeostasis of the entire cell. Tethering factors play pivotal roles in mediating the fusion of different transport vesicles, such as endosomes or autophagosomes with each other or with lysosomes. In this work, we uncover several new interactions between the endolysosomal tethering factors Rabenosyn-5 (Rbsn) and the HOPS and CORVET complexes. We find that Rbsn binds to the HOPS/CORVET complexes mainly via their shared subunit Vps18 and we mapped this interaction to the 773-854 region of Vps18. Based on genetic rescue experiments, the binding between Rbsn and Vps18 is required for endosomal transport and is dispensable for autophagy. Moreover, Vps18 seems to be important for β1 integrin recycling by binding to Rbsn and its known partner Vps45.