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J Neurosci August 21, 2013; 33 (34): 13621-38.

Signals governing the trafficking and mistrafficking of a ciliary GPCR, rhodopsin.

Lodowski KH , Lee R , Ropelewski P , Nemet I , Tian G , Imanishi Y .

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.

PubMed ID: 23966685
PMC ID: PMC3755712
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: atp1a1 eea1 gprc6a lamp1 rho rho.2 tbx2
Antibodies: Atp1a1 Ab3 Rho Ab3

Article Images: [+] show captions
References [+] :
Amaya, A method for generating transgenic frog embryos. 1999, Pubmed, Xenbase