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Published online
doi:10.1083/jcb.200702187
The Journal of Cell Biology, Vol. 179, No. 5, 965-980
The Rockefeller University Press, 0021-9525 $30.00
© Shah et al.
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Article

Adenovirus RID{alpha} regulates endosome maturation by mimicking GTP-Rab7



Ankur H. Shah1,2, Nicholas L. Cianciola1, Jeffrey L. Mills1, Frank D. Sönnichsen1, and Cathleen Carlin1,2,3

1 Department of Physiology and Biophysics, 2 Molecular Virology Training Program, and 3 Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106

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 {alpha} (RID{alpha}), 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{alpha} localizes to endocytic vesicles but is not homologous to Rab7 and is not catalytically active. We show that RID{alpha} compensates for reduced Rab7 or dominant-negative (DN) Rab7(T22N) expression. In vitro, Cu2+ binding to RID{alpha} residues His75 and His76 facilitates the RILP interaction. Site-directed mutagenesis of these His residues results in the loss of RID{alpha}–RILP interaction and RID{alpha} activity in cells. Additionally, expression of the RILP DN C-terminal region hinders RID{alpha} activity during an acute adenovirus infection. We conclude that RID{alpha} coordinates recruitment of these GTP-Rab7 effectors to compartments that would ordinarily be perceived as early endosomes, thereby promoting the degradation of selected cargo.

Abbreviations used in this paper: ANOVA, analysis of variance; DN, dominant negative; E3, early region 3; EGFR, EGF receptor; Hsp, heat-shock protein; LDL, low-density lipoprotein; MTOC, microtubule organizing center; MVB, multivesicular body; NMR, nuclear magnetic resonance; ORP, oxysterol-binding protein–related protein; RID, receptor internalization and degradation; RILP, Rab7-interacting lysosomal protein; TNFR1, TNF receptor 1; TRAIL-R, TNF-related apoptosis-inducing ligand receptor.


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