Scientific Reports 4: Article number: 7282 10.1038/srep07282; published online: December022014; updated: July152015
We did not cite a related study which demonstrated that RILP facilitates membrane recruitment of tethering HOPS complex and p150glued subunit of dynein complex, which is regulated by cholesterol sensor ORP1L (Reference 1). In that investigation, RILP interacts with HOPS complex and recruits subunits of HOPS complex to late endosomal membrane, which is consistent with our results. However, the data from van der Kant et al. suggested that multiple sites of RILP may bind to various subunits of HOPS complex, while our results strongly suggest that RILP preferentially interacts with accessory subunit VPS41, this discrepancy may be due to different approaches for testing the interaction (surface plasmon resonance (SPR) by van der Kant et al. vs GST-pulldown by us). We further characterized the region in VPS41 that is responsible for the interaction with RILP, and also functionally showed that the interaction of RILP with VPS41 is responsible for the endocytic trafficking of EGFR. We also revealed that the interaction of RILP with HOPS complex is independent of Rab7. We propose that RILP plays a role in facilitating the formation and stabilizing of Rab7-RILP-HOPS supercomplex on late endosomal membranes. Together with the results by Kant et al, RILP interaction with HOPS complex is a novel mechanism for regulating endosomal trafficking.
References
- van der Kant R. et al. Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L. J. Cell Sci. 126, 3462–3474 (2013) [DOI] [PubMed] [Google Scholar]