1. Disruption of the Coxsackievirus and Adenovirus Receptor-Homodimeric Interaction Triggers Lipid Microdomain- and Dynamin-dependent Endocytosis and Lysosomal Targeting
- Author
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Sara Salinas, Eric J. Kremer, Charleine Zussy, Madeline Parsons, Daniel Henaff, Guillermo Menendez, Giampietro Schiavo, Fabien Loustalot, Penny E. Morton, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
- Subjects
viruses ,Endocytic cycle ,Ligands ,Biochemistry ,Mice ,0302 clinical medicine ,Fluorescent Antibody Technique, Indirect ,Internalization ,Lipid raft ,Cells, Cultured ,media_common ,Neurons ,0303 health sciences ,Microscopy, Confocal ,biology ,virus diseases ,Endocytosis ,Enterovirus B, Human ,Cell biology ,Clathrin Heavy Chains ,Electrophoresis, Polyacrylamide Gel ,RNA Interference ,Intracellular ,Protein Binding ,Dynamins ,Coxsackie and Adenovirus Receptor-Like Membrane Protein ,endocrine system ,media_common.quotation_subject ,Molecular Sequence Data ,education ,Coxsackievirus ,Microbiology ,Adenoviridae ,03 medical and health sciences ,Membrane Microdomains ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,Dynamin ,Lipid microdomain ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Molecular biology ,Protein Multimerization ,Lysosomes ,human activities ,030217 neurology & neurosurgery - Abstract
International audience; The coxsackievirus and adenovirus receptor (CAR) serves as a docking factor for some adenovirus (AdV) types and group B coxsackieviruses. Its role in AdV internalisation is unclear as studies suggest that its intracellular domain is dispensable for some AdV serotype infection. We previously showed that in motor neurons, an adenovirus induced CAR internalisation, and their co-transport in axons, suggesting that CAR was linked to endocytic and long-range transport machineries. Here, we characterised the mechanisms of CAR endocytosis in neurons and neuronal cells. We show that ligands that disrupted the homodimeric CAR interactions in its D1 domains triggered an internalisation cascade involving sequences in its intracellular tail. CAR-associated internalisation was also lipid microdomain, actin- and dynamin-dependent, and subsequently followed by CAR degradation by lysosomes.
- Published
- 2014
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