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Originally published In Press as doi:10.1074/jbc.M111937200 on December 21, 2001

J. Biol. Chem., Vol. 277, Issue 10, 7897-7904, March 8, 2002
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Interaction of the Poliovirus Receptor CD155 with the Dynein Light Chain Tctex-1 and Its Implication for Poliovirus Pathogenesis*

Steffen MuellerDagger , Xuemei Cao§, Reinhold Welker, and Eckard Wimmer

From the Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794

The cellular receptor for poliovirus CD155 (or PVR) is the founding member of a new class of membrane-associated immunoglobulin-like proteins, which include the mouse tumor-associated antigen E4 (Tage4) and three proteins termed "nectins." Using a yeast two-hybrid screen we have discovered that the cytoplasmic domain of CD155 associates strongly and specifically with Tctex-1, a light chain of the dynein motor complex, the latter representing the major driving force for retrograde transport of endocytic vesicles and membranous organelles. We confirmed the interaction biochemically and by co-immunoprecipitation, and we mapped the Tctex-1 binding site to a SKCSR motif within the juxtamembrane region of CD155. Tctex-1 immunoreactivity was detected in mouse sciatic nerve and spinal cord (two tissues of central importance for poliovirus pathogenesis) in punctate, possibly vesicular, patterns. We propose that the cytoplasmic domain may target CD155-containing endocytic vesicles to the microtubular network.

Neurotropic viruses like poliovirus, herpesvirus, rabies virus, and pseudorabies virus all utilize neuronal retrograde transport to invade the central nervous system. Association with Tctex-1 and, hence, with the dynein motor complex may offer an explanation for how poliovirus hijacks the cellular transport machinery to retrogradely ascend along the axon to the neuronal cell body.

* This work was supported in part by Public Health Service Grants A1-15122 and R01AT-32100 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a doctoral fellowship of Boehringer Ingelheim Fonds, Heidesheim, Germany.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) U56255.

§ Current address: Pfizer Global Research & Development, Groton, CT 06340.

To whom correspondence should be addressed: Dept. of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794. Tel.: 631-632-8787; Fax: 631-632-8891; E-mail: ewimmer@ms.cc.sunysb.ed.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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