Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis.
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.
Mueller
Steffen
S
Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794, USA.
Cao
Xuemei
X
Welker
Reinhold
R
Wimmer
Eckard
E
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D015723:Gene Library; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007763:Lac Operon; D008565:Membrane Proteins; D051379:Mice; D008868:Microtubule Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D010957:Plasmids / Q000378:metabolism; D017955:Poliovirus / Q000378:metabolism* / Q000472:pathogenicity*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D056427:t-Complex Genome Region
D018076:DNA, Complementary; C533386:Dynlt1b protein, mouse; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor; D005982:Glutathione Transferase; D004398:Dyneins