Reference Report

Reference
Citation	Cheli, V.T., Daniels, R.W., Godoy, R., Hoyle, D.J., Kandachar, V., Starcevic, M., Martinez-Agosto, J.A., Poole, S., DiAntonio, A., Lloyd, V.K., Chang, H.C., Krantz, D.E., Dell'angelica, E.C. (2010). Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency. Hum. Mol. Genet. 19(5): 861--878. (Export to RIS)
FlyBase ID	FBrf0209903
Publication Type	Research paper
PubMed ID	20015953
PubMed Abstract	Biogenesis of lysosome-related organelles complex 1 (BLOC-1) is a protein complex formed by the products of eight distinct genes. Loss-of-function mutations in two of these genes, DTNBP1 and BLOC1S3, cause Hermansky-Pudlak syndrome, a human disorder characterized by defective biogenesis of lysosome-related organelles. In addition, haplotype variants within the same two genes have been postulated to increase the risk of developing schizophrenia. However, the molecular function of BLOC-1 remains unknown. Here, we have generated a fly model of BLOC-1 deficiency. Mutant flies lacking the conserved Blos1 subunit displayed eye pigmentation defects due to abnormal pigment granules, which are lysosome-related organelles, as well as abnormal glutamatergic transmission and behavior. Epistatic analyses revealed that BLOC-1 function in pigment granule biogenesis requires the activities of BLOC-2 and a putative Rab guanine-nucleotide-exchange factor named Claret. The eye pigmentation phenotype was modified by misexpression of proteins involved in intracellular protein trafficking; in particular, the phenotype was partially ameliorated by Rab11 and strongly enhanced by the clathrin-disassembly factor, Auxilin. These observations validate Drosophila melanogaster as a powerful model for the study of BLOC-1 function and its interactions with modifier genes.
DOI	10.1093/hmg/ddp555
Related Publication(s)
Supplementary material	Supplementary Data. [FBrf0210495]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Hum. Mol. Genet.
Title	Human Molecular Genetics
Publication Year	1992-
ISBN/ISSN	0964-6906
Data from Reference
Alleles (31)
	Arfip^EY11874 aux^{CJ.DLL.DPF.Scer\UAS.T:Disc\RFP-mRFP} aux^{CJ.DLL.Scer\UAS.T:Disc\RFP-mRFP} aux^{CJ.DPF.Scer\UAS.T:Disc\RFP-mRFP} aux^{CJ.Scer\UAS.T:Disc\RFP-mRFP} aux^{FL.Scer\UAS.T:Disc\RFP-mRFP} aux^G257E aux^I670K aux^L78H aux^{ΔC.Scer\UAS.T:Disc\RFP-mRFP} aux^{ΔJ.Scer\UAS.T:Disc\RFP-mRFP} blos1^ex2 blos1^ex65 blos1^Scer\UAS.cCa ca¹ cm¹ g² g^53d ltd¹ or^49h p^p Rab11^d01994 Rab11^d04643 Rabex-5^EP681a rb¹ Scer\GAL4^GMR.PF T:Disc\RFP^mRFP w^+mC w^Scer\UAS.cTa w^unspecified y^+mDint2
Constructs (11)
	P{GAL4-ninaE.GMR} P{GMR-GAL4.w^-.C} P{UAS-aux.mRFP.CJ.DLL.DPF} P{UAS-aux.mRFP.CJ.DLL} P{UAS-aux.mRFP.CJ.DPF} P{UAS-aux.mRFP.CJ} P{UAS-aux.mRFP.FL} P{UAS-aux.mRFP.ΔC} P{UAS-aux.mRFP.ΔJ} P{UAS-blos1.C} P{UAS-w.T}
Genes (28)
	Arfip aux blos1 blos2 blos3 blos4 ca CG5745 CG5916 CG12241 cm dysb g ltd muted or p pallidin Rab5 Rab7 Rab11 Rabex-5 rb Scer\GAL4 snapin w wkd y
Insertions (9)
	P{EP}Rabex-5^EP681a P{EPgy2}Arfip^EY11874 P{EPgy2}blos1^EY06269 P{EPgy2}CG5903^EY11938 P{EPgy2}EY00704 P{EPgy2}EY16920 P{XP}Rab11^d01994 P{XP}Rab11^d04643 PBac{WH}CG5342^f05247
Natural transposons (1)
	P-element