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dc.contributor.authorGleich, Kurten
dc.contributor.authorDesmond, Michael Jen
dc.contributor.authorLee, Darrenen
dc.contributor.authorBerkovic, Samuel Fen
dc.contributor.authorDibbens, Leanne Men
dc.contributor.authorKaterelos, Marinaen
dc.contributor.authorBayly, Marta Aen
dc.contributor.authorFraser, Scott Aen
dc.contributor.authorMartinello, Paulen
dc.contributor.authorVears, Danya Fen
dc.contributor.authorMount, Peteren
dc.contributor.authorPower, David Anthonyen
dc.identifier.citationBioresearch Open Access; 2(1): 40-6en
dc.description.abstractMutations of the intrinsic lysosomal membrane protein SCARB2 cause action myoclonus-renal failure syndrome (AMRF syndrome), a rare disease characterized by renal and neurological manifestations. In this study, examination of Cos7 cells transfected with SCARB2 cDNA derived from two patients with AMRF syndrome showed that the resultant protein was truncated and was not incorporated into vesicular structures, as occurred with full-length SCARB2 cDNA. Mutant SCARB2 protein failed to colocalize with lysosomes and was found in the endoplasmic reticulum or the cytosol indicating a loss of function. Cultured skin fibroblast and Epstein-Barr virus-transformed lymphoblastoid B cell lines (LCLs) were created from these two patients. Despite the loss of SCARB2 function, studies with lysosomal-associated membrane protein (LAMP) 1 and LAMP2 demonstrated normal lysosomal numbers in fibroblasts and LCLs. Immunofluorescence microscopy using anti-LAMP1 and anti-LAMP2 antibodies also showed normal lysosomal structures in fibroblasts. There was no change in the morphology of fibroblasts examined by electron microscopy compared with cells from unaffected individuals. By contrast, LCLs from individuals bearing SCARB2 mutations had large intracellular vesicles that resembled autophagosomes and contained heterogeneous cellular debris. Some of the autophagosomes were seen to be extruding cellular contents into the media. Furthermore, LCLs had elevated levels of microtubule-associated protein light chain 3-II, consistent with increased autophagy. These data demonstrate that SCARB2 mutations are associated with an inability to process autophagosomes in B lymphocytes, suggesting a novel function for SCARB2 in immune function.en
dc.subject.othercellular biologyen
dc.titleAbnormal Processing of Autophagosomes in Transformed B Lymphocytes from SCARB2-Deficient Subjects.en
dc.typeJournal Articleen
dc.identifier.journaltitleBioResearch open accessen
dc.identifier.affiliationThe Institute for Breathing and Sleep, Austin Health , Heidelberg, Australia .en
Appears in Collections:Journal articles

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