Rab6 Regulation of Rhodopsin Transport inDrosophila

Shetty, Kiran M.; Kurada, Phani; O'Tousa, Joseph E.

doi:10.1074/jbc.273.32.20425

Cited by 69 publications

(55 citation statements)

References 48 publications

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“…It has also been demonstrated that manipulation of Rab6 function through expressing its GTP-bound, GDP-bound or guanidine nucleotide deficient mutants inhibits transport of the plasma membrane proteins hemagglutinin protein and CFTR in mammalian cells and rhodopsin in Drosophila [42,45,46]. Consistent with the role of Rab6 in the plasma membrane targeting, our data indicate that Rab6 is required for the transport to the cell surface of some GPCRs.…”

Section: Discussionsupporting

confidence: 85%

Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases

Dong

2007

Cellular Signalling

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Three Rab GTPases, Rab1, Rab2 and Rab6, are involved in protein transport between the endoplasmic reticulum (ER) and the Golgi. Whereas Rab1 regulates the anterograde ER-to-Golgi transport, Rab2 and Rab6 coordinate the retrograde Golgi-to-ER transport. We have previously demonstrated that Rab1 differentially modulates the export trafficking of distinct G protein-coupled receptors (GPCRs). In this report, we determined the role of Rab2 and Rab6 in the cell surface expression and signaling of α 2B -adrenergic (α 2B -AR), β 2 -AR and angiotensin II type 1 receptors (AT1R). Expression of the GTP-bound mutant Rab2Q65L significantly attenuated the cell-surface expression of both α 2B -AR and β 2 -AR, whereas the GTP-bound mutant Rab6Q72L selectively inhibited the transport of β 2 -AR, but not α 2B -AR. Similar results were obtained by siRNA-mediated selective knockdown of endogenous Rab2 and Rab6. Consistently, Rab2Q65L and Rab2 siRNA inhibited α 2B -AR and β 2 -AR signaling measured as ERK1/2 activation and cAMP production, respectively, whereas Rab6Q72L and Rab6 siRNA reduced signaling of β 2 -AR, but not α 2B -AR. Similar to the β 2 -AR, AT1R expression at the cell surface and AT1R-promoted inositol phosphate accumulation were inhibited by Rab6Q72L. Furthermore, the nucleotide-free mutant Rab6N126I selectively attenuated the cell-surface expression of β 2 -AR and AT1R, but not α 2B -AR. These data demonstrate that Rab2 and Rab6 differentially influence anterograde transport and signaling of GPCRs. These data also provide the first evidence indicating that Rab6-coordinated retrograde transport selectively modulates intracellular trafficking and signaling of GPCRs.

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Section: Discussionsupporting

confidence: 85%

Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases

Dong

2007

Cellular Signalling

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“…This latter aspect of the cnx phenotype most likely reflects an additional role of calnexin as a Ca 2+ buffer [70]. Rab6 also appears to be required for rhodopsin maturation, since expression of a dominant negative form of Rab6 causes defective rhodopsin maturation, and trafficking and triggers retinal degeneration [64]. Taken together, these findings demonstrate that disruption in rhodopsin maturation leads to retinal degeneration.…”

Section: Retinal Degenerationmentioning

confidence: 89%

“…Rab1 is required for rhodopsin transport between the ER and Golgi complex [63], Rab6 functions in the transport through the ER-Golgi complex [64], and Rab11 mediates post-Golgi translocation of rhodopsin [65]. The function of Rab6 may be rhodopsin-specific, whereas Rab1 and Rab11 operate more generally in the trafficking of membrane proteins in photoreceptor cells [63][64][65].…”

Section: Maturation Of Rhodopsinmentioning

confidence: 99%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

257

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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“…72 Mature Rh1 is transported through the Golgi. The post-Golgi trafficking is orchestrated by monomeric G-proteins including Rab 6 52 and Rab11. 53 Finally, Rh1 is delivered to and inserted into the rhabdomeric membrane.…”

Section: +mentioning

confidence: 99%

Molecular genetics of retinal degeneration: A Drosophila perspective

Shieh

2011

fly

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Rab6 Regulation of Rhodopsin Transport inDrosophila

Cited by 69 publications

References 48 publications

Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases

Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases

Phototransduction and retinal degeneration in Drosophila

Molecular genetics of retinal degeneration: A Drosophila perspective

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