TRP and Rhodopsin Transport Depends on Dual XPORT ER Chaperones Encoded by an Operon

• Trafficking of TRP and rhodopsin depends on the bicistronic xport locus
• XPORT-A and XPORT-B coordinately contribute to ER exit of TRP and rhodopsin
• Loss of XPORT-A or XPORT-B mimics the trp ERG and retinal degeneration phenotypes
• XPORT-B forms a complex in vivo with an HSP70 protein and rhodopsin

SummaryTRP channels and G protein-coupled receptors (GPCRs) play critical roles in sensory reception. However, the identities of the chaperones that assist GPCRs in translocating from the endoplasmic reticulum (ER) are limited, and TRP ER chaperones are virtually unknown. The one exception for TRPs is Drosophila XPORT. Here, we show that the xport locus is bicistronic and encodes unrelated transmembrane proteins, which enable the signaling proteins that initiate and culminate phototransduction, rhodopsin 1 (Rh1) and TRP, to traffic to the plasma membrane. XPORT-A and XPORT-B are ER proteins, and loss of either has a profound impact on TRP and Rh1 targeting to the light-sensing compartment of photoreceptor cells. XPORT-B complexed in vivo with the Drosophila homolog of the mammalian HSP70 protein, GRP78/BiP, which, in turn, associated with Rh1. Our work highlights a coordinated network of chaperones required for the biosynthesis of the TRP channel and rhodopsin in Drosophila photoreceptor cells.

Graphical AbstractFigure optionsDownload as PowerPoint slide