Flies used to test impact of retinal disease-relevant mutations on function of Crumbs family proteins

Pellikka M, Tepass U. Unique cell biological profiles of retinal disease-causing missense mutations in the polarity protein crumbs. J Cell Sci. 2017 May 17. pii: jcs.197178. PMID: 28515229.

From the abstract: "Mutations in human CRB1 are a major cause of retinal disease that lead to blindness. CRB1 is a transmembrane protein found in the inner segment of photoreceptor cells (PRCs) and the apical membrane of Müller glia. The function of the extracellular region of CRB1 is poorly understood although more than 80 disease-causing missense mutations have been mapped to it. We have recreated four mutations in Drosophila Crumbs (Crb) that affect different extracellular domains. ... The mutant Crb isoforms showed a remarkable diversity in protein abundance, subcellular distribution, and ability to rescue the lack of endogenous Crb, elicit a gain-of-function phenotype, or promote PRC degeneration. Interestingly, although expression of mutant isoforms rescued developmental defects of crb mutants substantially, they accelerated PRC degeneration compared to retinas that lack Crb ... Several Crb mutant proteins accumulated abnormally in the rhabdomere and affected rhodopsin trafficking, suggesting that abnormal rhodopsin physiology contributes to Crb/CRB1-dependent retinal degeneration."

Retinal degeneration-related fly study. Recent report.

Lee J, Song M, Hong S. Negative regulation of the novel norpA(P24) suppressor, diehard4, in the endo-lysosomal trafficking underlies photoreceptor cell degeneration. PLoS Genet. 2013 Jun;9(6):e1003559. doi: 10.1371/journal.pgen.1003559. PMID: 23754968; PMCID: PMC3674991.

The fly & retinal degeneration--recent review

Xiong B, Bellen HJ. Rhodopsin homeostasis and retinal degeneration: lessons from the fly. Trends Neurosci. 2013 Sep 5. PMID: 24012059.

From the abstract: "We review here the molecular signals involved in Rh homeostasis and the mechanisms underlying retinal degeneration in flies, and discuss possible links to human diseases."

Retinal degeneration/dystrophy & the fly. Recent report.

Lee J, Song M, Hong S. Negative Regulation of the Novel norpA(P24) Suppressor, diehard4, in the Endo-lysosomal Trafficking Underlies Photoreceptor Cell Degeneration. PLoS Genet. 2013 un;9(6):e1003559. Epub 2013 Jun 6. PMID: 23754968.

From the abstract:  "Our results demonstrate the existence of negative regulation in vesicular traffic between endosomes and lysosomes. We anticipate that the identification of additional components and an in-depth description of this specific molecular machinery will aid in therapeutic interventions of various retinal dystrophies and GPCR-related human diseases."