title: Disruption of the coxsackievirus and adenovirus receptor-homodimeric interaction triggers lipid microdomain- and dynamin-dependent endocytosis and lysosomal targeting.
abstract: The coxsackievirus and adenovirus receptor (CAR) serves as a docking factor for some adenovirus (AdV) types and group B coxsackieviruses. Its role in AdV internalization is unclear as studies suggest that its intracellular domain is dispensable for some AdV infection. We previously showed that in motor neurons, AdV induced CAR internalization and co-transport in axons, suggesting that CAR was linked to endocytic and long-range transport machineries. Here, we characterized the mechanisms of CAR endocytosis in neurons and neuronal cells. We found that CAR internalization was lipid microdomain-, actin-, and dynamin-dependent, and subsequently followed by CAR degradation in lysosomes. Moreover, ligands that disrupted the homodimeric CAR interactions in its D1 domains triggered an internalization cascade involving sequences in its intracellular tail.
authors.affiliation: From the Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Montpellier, Universités de Montpellier I & II, Montpellier, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Salinas
authors.forename: Charleine
authors.initials: C
authors.lastname: Zussy
authors.forename: Fabien
authors.initials: F
authors.lastname: Loustalot
authors.forename: Daniel
authors.initials: D
authors.lastname: Henaff
authors.forename: Guillermo
authors.initials: G
authors.lastname: Menendez
authors.forename: Penny E
authors.initials: PE
authors.lastname: Morton
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D029822:Enterovirus B, Human / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D034622:RNA Interference
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D008024:Ligands; D033922:Clathrin Heavy Chains; D034281:Dynamins
keywords: Adenovirus; Axonal Transport; CAR; Endocytosis; Lipid Raft; Lysosomes; Neurons