RT Journal Article SR Electronic T1 Signals Governing the Trafficking and Mistrafficking of a Ciliary GPCR, Rhodopsin JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 13621 OP 13638 DO 10.1523/JNEUROSCI.1520-13.2013 VO 33 IS 34 A1 Kerrie H. Lodowski A1 Richard Lee A1 Philip Ropelewski A1 Ina Nemet A1 Guilian Tian A1 Yoshikazu Imanishi YR 2013 UL http://www.jneurosci.org/content/33/34/13621.abstract AB Rhodopsin is a cilia-specific GPCR essential for vision. Rhodopsin mislocalization is associated with blinding diseases called retinal ciliopathies. The mechanism by which rhodopsin mislocalizes in rod photoreceptor neurons is not well understood. Therefore, we investigated the roles of trafficking signals in rhodopsin mislocalization. Rhodopsin and its truncation mutants were fused to a photoconvertible fluorescent protein, Dendra2, and expressed in Xenopus laevis rod photoreceptors. Photoconversion of Dendra2 causes a color change from green to red, enabling visualization of the dynamic events associated with rhodopsin trafficking and renewal. We found that rhodopsin mislocalization is a facilitated process for which a signal located within 322–326 aa (CCGKN) is essential. An additional signal within 327–336 aa further facilitated the mislocalization. This collective mistrafficking signal confers toxicity to rhodopsin and causes mislocalization when the VXPX cilia-targeting motif is absent. We also determined that the VXPX motif neutralizes this mistrafficking signal, enhances ciliary targeting at least 10-fold, and accelerates trafficking of post-Golgi vesicular structures. In the absence of the VXPX motif, mislocalized rhodopsin is actively cleared through secretion of vesicles into the extracellular milieu. Therefore, this study unveiled the multiple roles of trafficking signals in rhodopsin localization and renewal.