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Adenovirus RID
regulates endosome maturation by mimicking GTP-Rab7
Correspondence to Cathleen Carlin: cathleen.carlin{at}case.edu
The small guanosine triphosphatase Rab7 regulates late endocytic trafficking. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are guanosine triphosphate (GTP)–Rab7 effectors that instigate minus end–directed microtubule transport. We demonstrate that RILP and ORP1L both interact with the group C adenovirus protein known as receptor internalization and degradation
(RID
), which was previously shown to clear the cell surface of several membrane proteins, including the epidermal growth factor receptor and Fas (Carlin, C.R., A.E. Tollefson, H.A. Brady, B.L. Hoffman, and W.S. Wold. 1989. Cell. 57:135–144; Shisler, J., C. Yang, B. Walter, C.F. Ware, and L.R. Gooding. 1997. J. Virol. 71:8299–8306). RID
localizes to endocytic vesicles but is not homologous to Rab7 and is not catalytically active. We show that RID
compensates for reduced Rab7 or dominant-negative (DN) Rab7(T22N) expression. In vitro, Cu2+ binding to RID
residues His75 and His76 facilitates the RILP interaction. Site-directed mutagenesis of these His residues results in the loss of RID
–RILP interaction and RID
activity in cells. Additionally, expression of the RILP DN C-terminal region hinders RID
activity during an acute adenovirus infection. We conclude that RID
coordinates recruitment of these GTP-Rab7 effectors to compartments that would ordinarily be perceived as early endosomes, thereby promoting the degradation of selected cargo.
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