Disruption of the coxsackievirus and adenovirus receptor- homodimeric interaction triggers lipid microdomain- and dynamin-dependent endocytosis and lysosomal targeting

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.