Neurexin Regulates Visual Function via Mediating Retinoid Transport to Promote Rhodopsin Maturation

SummaryNeurexins are cell adhesion molecules involved in synapse formation and synaptic regulation. Mutations in the neurexin genes are linked to a number of neurodevelopmental disorders such as autism. Here, we show that the Drosophila homolog of α-Neurexin is critical for fly visual function. Lack of Neurexin leads to significantly impaired visual function due to reduced rhodopsin levels. We show that the decreased chromophore levels cause deficits in rhodopsin maturation and that Neurexin is required for retinoid transport. Using yeast two-hybrid screening, we identify that Neurexin interacts with apolipoprotein I (ApoL I), a product generated by cleavage of retinoid- and fatty acid-binding glycoprotein (RFABG) that functions in retinoid transport. Finally, we demonstrate that Neurexin is essential for the apolipoproteins level. Our results reveal a role for Neurexin in mediating retinoid transport and subsequent rhodopsin maturation and suggest that Neurexin regulates lipoprotein function.

► neurexin mutant shows significant reduced rhodopsin levels ► Deficit in Rh1 maturation in neurexin mutant is due to reduced chromophore levels ► Neurexin binds and stabilizes apolipoprotein I ► Neurexin mediates retinoid transport via regulating ApoL protein levels